WO2022047325A1 - Ciblage de tmg4 pour le traitement du cancer de la prostate - Google Patents
Ciblage de tmg4 pour le traitement du cancer de la prostate Download PDFInfo
- Publication number
- WO2022047325A1 WO2022047325A1 PCT/US2021/048273 US2021048273W WO2022047325A1 WO 2022047325 A1 WO2022047325 A1 WO 2022047325A1 US 2021048273 W US2021048273 W US 2021048273W WO 2022047325 A1 WO2022047325 A1 WO 2022047325A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- tgm4
- cells
- antibody
- subject
- prostate cancer
- Prior art date
Links
- 206010060862 Prostate cancer Diseases 0.000 title claims abstract description 55
- 208000000236 Prostatic Neoplasms Diseases 0.000 title claims abstract description 55
- 230000008685 targeting Effects 0.000 title abstract description 4
- 102100038103 Protein-glutamine gamma-glutamyltransferase 4 Human genes 0.000 claims abstract description 126
- 238000000034 method Methods 0.000 claims abstract description 84
- 239000003098 androgen Substances 0.000 claims abstract description 57
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 18
- 238000009169 immunotherapy Methods 0.000 claims abstract description 16
- 150000003384 small molecules Chemical class 0.000 claims abstract description 10
- 238000002512 chemotherapy Methods 0.000 claims abstract description 5
- 238000001959 radiotherapy Methods 0.000 claims abstract description 5
- 238000002679 ablation Methods 0.000 claims abstract description 4
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 4
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 115
- 230000014509 gene expression Effects 0.000 claims description 98
- 108090000623 proteins and genes Proteins 0.000 claims description 66
- 238000009167 androgen deprivation therapy Methods 0.000 claims description 53
- 229960005486 vaccine Drugs 0.000 claims description 34
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims description 33
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims description 33
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims description 33
- 102000004169 proteins and genes Human genes 0.000 claims description 27
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 26
- 206010028980 Neoplasm Diseases 0.000 claims description 25
- 239000000427 antigen Substances 0.000 claims description 25
- 108091007433 antigens Proteins 0.000 claims description 25
- 102000036639 antigens Human genes 0.000 claims description 25
- 238000011282 treatment Methods 0.000 claims description 24
- 239000000556 agonist Substances 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 20
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 claims description 15
- 230000004068 intracellular signaling Effects 0.000 claims description 12
- 210000000822 natural killer cell Anatomy 0.000 claims description 12
- 102000040430 polynucleotide Human genes 0.000 claims description 12
- 108091033319 polynucleotide Proteins 0.000 claims description 12
- 239000002157 polynucleotide Substances 0.000 claims description 12
- -1 0X40 Proteins 0.000 claims description 10
- 239000012634 fragment Substances 0.000 claims description 10
- 230000004083 survival effect Effects 0.000 claims description 10
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 claims description 9
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 claims description 9
- 229940045513 CTLA4 antagonist Drugs 0.000 claims description 9
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 claims description 9
- 239000003153 chemical reaction reagent Substances 0.000 claims description 9
- 102000039446 nucleic acids Human genes 0.000 claims description 9
- 108020004707 nucleic acids Proteins 0.000 claims description 9
- 150000007523 nucleic acids Chemical class 0.000 claims description 9
- 108010074708 B7-H1 Antigen Proteins 0.000 claims description 8
- 108010021064 CTLA-4 Antigen Proteins 0.000 claims description 8
- 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 claims description 8
- 101710089372 Programmed cell death protein 1 Proteins 0.000 claims description 8
- 229940126547 T-cell immunoglobulin mucin-3 Drugs 0.000 claims description 8
- 102100024834 T-cell immunoreceptor with Ig and ITIM domains Human genes 0.000 claims description 8
- 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 claims description 8
- 230000000259 anti-tumor effect Effects 0.000 claims description 8
- 239000013598 vector Substances 0.000 claims description 8
- 101150013553 CD40 gene Proteins 0.000 claims description 7
- 101710083479 Hepatitis A virus cellular receptor 2 homolog Proteins 0.000 claims description 7
- 101000831007 Homo sapiens T-cell immunoreceptor with Ig and ITIM domains Proteins 0.000 claims description 7
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 claims description 7
- 239000002671 adjuvant Substances 0.000 claims description 7
- 238000011319 anticancer therapy Methods 0.000 claims description 7
- 230000036039 immunity Effects 0.000 claims description 7
- 230000001580 bacterial effect Effects 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 239000013603 viral vector Substances 0.000 claims description 6
- 102100036166 C-X-C chemokine receptor type 1 Human genes 0.000 claims description 5
- 241000701022 Cytomegalovirus Species 0.000 claims description 5
- 108020004414 DNA Proteins 0.000 claims description 5
- 101000947174 Homo sapiens C-X-C chemokine receptor type 1 Proteins 0.000 claims description 5
- 108090001007 Interleukin-8 Proteins 0.000 claims description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 4
- 101000904173 Homo sapiens Progonadoliberin-1 Proteins 0.000 claims description 4
- 102100024028 Progonadoliberin-1 Human genes 0.000 claims description 4
- 101000996723 Sus scrofa Gonadotropin-releasing hormone receptor Proteins 0.000 claims description 4
- XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 claims description 4
- 238000011474 orchiectomy Methods 0.000 claims description 4
- 241001232026 Actium Species 0.000 claims description 3
- 241000702421 Dependoparvovirus Species 0.000 claims description 3
- 241000713666 Lentivirus Species 0.000 claims description 3
- 241000186781 Listeria Species 0.000 claims description 3
- 229940124041 Luteinizing hormone releasing hormone (LHRH) antagonist Drugs 0.000 claims description 3
- 229910052765 Lutetium Inorganic materials 0.000 claims description 3
- 241000711408 Murine respirovirus Species 0.000 claims description 3
- 241000700618 Vaccinia virus Species 0.000 claims description 3
- 241000700605 Viruses Species 0.000 claims description 3
- 230000002280 anti-androgenic effect Effects 0.000 claims description 3
- 239000000051 antiandrogen Substances 0.000 claims description 3
- 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 claims description 3
- 238000001574 biopsy Methods 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 230000000903 blocking effect Effects 0.000 claims description 3
- 229940127089 cytotoxic agent Drugs 0.000 claims description 3
- 239000002254 cytotoxic agent Substances 0.000 claims description 3
- OHSVLFRHMCKCQY-UHFFFAOYSA-N lutetium atom Chemical compound [Lu] OHSVLFRHMCKCQY-UHFFFAOYSA-N 0.000 claims description 3
- 108020004999 messenger RNA Proteins 0.000 claims description 3
- 230000037361 pathway Effects 0.000 claims description 3
- 238000001356 surgical procedure Methods 0.000 claims description 3
- 238000003786 synthesis reaction Methods 0.000 claims description 3
- 241000701161 unidentified adenovirus Species 0.000 claims description 3
- 241001430294 unidentified retrovirus Species 0.000 claims description 3
- 101000666131 Homo sapiens Protein-glutamine gamma-glutamyltransferase 4 Proteins 0.000 claims 15
- 102100023990 60S ribosomal protein L17 Human genes 0.000 claims 2
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 claims 2
- 108010058716 transglutaminase 4 Proteins 0.000 abstract description 115
- 210000004027 cell Anatomy 0.000 description 47
- 210000002307 prostate Anatomy 0.000 description 41
- 102100035703 Prostatic acid phosphatase Human genes 0.000 description 27
- 102100025137 Early activation antigen CD69 Human genes 0.000 description 26
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 26
- 108010043671 prostatic acid phosphatase Proteins 0.000 description 26
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 24
- 201000005825 prostate adenocarcinoma Diseases 0.000 description 24
- 101100260031 Homo sapiens TBX21 gene Proteins 0.000 description 22
- 102100036840 T-box transcription factor TBX21 Human genes 0.000 description 22
- 235000018102 proteins Nutrition 0.000 description 20
- 210000001519 tissue Anatomy 0.000 description 20
- 238000004458 analytical method Methods 0.000 description 19
- 102100038358 Prostate-specific antigen Human genes 0.000 description 18
- 239000005090 green fluorescent protein Substances 0.000 description 18
- 241001529936 Murinae Species 0.000 description 16
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 16
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 15
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 15
- 238000000338 in vitro Methods 0.000 description 15
- 210000003734 kidney Anatomy 0.000 description 15
- 102100027207 CD27 antigen Human genes 0.000 description 14
- 101000914511 Homo sapiens CD27 antigen Proteins 0.000 description 14
- 210000004072 lung Anatomy 0.000 description 13
- 230000004044 response Effects 0.000 description 13
- 210000002966 serum Anatomy 0.000 description 13
- 241000699670 Mus sp. Species 0.000 description 12
- 101150107779 Tgm4 gene Proteins 0.000 description 12
- 230000005875 antibody response Effects 0.000 description 12
- 201000011510 cancer Diseases 0.000 description 12
- 210000004185 liver Anatomy 0.000 description 12
- 230000000638 stimulation Effects 0.000 description 12
- 229960003604 testosterone Drugs 0.000 description 12
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 description 11
- 102100040678 Programmed cell death protein 1 Human genes 0.000 description 11
- 230000008859 change Effects 0.000 description 11
- 239000012528 membrane Substances 0.000 description 11
- 210000002919 epithelial cell Anatomy 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 8
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 8
- 101001068133 Homo sapiens Hepatitis A virus cellular receptor 2 Proteins 0.000 description 8
- 102000008070 Interferon-gamma Human genes 0.000 description 8
- 108010074328 Interferon-gamma Proteins 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 230000004913 activation Effects 0.000 description 8
- 210000001072 colon Anatomy 0.000 description 8
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 8
- 238000000684 flow cytometry Methods 0.000 description 8
- 229960003130 interferon gamma Drugs 0.000 description 8
- 210000001616 monocyte Anatomy 0.000 description 8
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 8
- 239000002953 phosphate buffered saline Substances 0.000 description 8
- 210000003079 salivary gland Anatomy 0.000 description 8
- SGKRLCUYIXIAHR-AKNGSSGZSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O SGKRLCUYIXIAHR-AKNGSSGZSA-N 0.000 description 7
- 102000004127 Cytokines Human genes 0.000 description 7
- 108090000695 Cytokines Proteins 0.000 description 7
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 description 7
- 101150087808 MSMB gene Proteins 0.000 description 7
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 7
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 7
- 229960003722 doxycycline Drugs 0.000 description 7
- 230000004547 gene signature Effects 0.000 description 7
- 238000001114 immunoprecipitation Methods 0.000 description 7
- PGHMRUGBZOYCAA-UHFFFAOYSA-N ionomycin Natural products O1C(CC(O)C(C)C(O)C(C)C=CCC(C)CC(C)C(O)=CC(=O)C(C)CC(C)CC(CCC(O)=O)C)CCC1(C)C1OC(C)(C(C)O)CC1 PGHMRUGBZOYCAA-UHFFFAOYSA-N 0.000 description 7
- PGHMRUGBZOYCAA-ADZNBVRBSA-N ionomycin Chemical compound O1[C@H](C[C@H](O)[C@H](C)[C@H](O)[C@H](C)/C=C/C[C@@H](C)C[C@@H](C)C(/O)=C/C(=O)[C@@H](C)C[C@@H](C)C[C@@H](CCC(O)=O)C)CC[C@@]1(C)[C@@H]1O[C@](C)([C@@H](C)O)CC1 PGHMRUGBZOYCAA-ADZNBVRBSA-N 0.000 description 7
- 229920001481 poly(stearyl methacrylate) Polymers 0.000 description 7
- 230000037452 priming Effects 0.000 description 7
- 208000023958 prostate neoplasm Diseases 0.000 description 7
- 238000007619 statistical method Methods 0.000 description 7
- 238000011830 transgenic mouse model Methods 0.000 description 7
- 102000008096 B7-H1 Antigen Human genes 0.000 description 6
- 241000699660 Mus musculus Species 0.000 description 6
- 101100348669 Mus musculus Nkx3-1 gene Proteins 0.000 description 6
- 239000011324 bead Substances 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 6
- 230000016396 cytokine production Effects 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 6
- 238000002955 isolation Methods 0.000 description 6
- 239000013641 positive control Substances 0.000 description 6
- 210000003491 skin Anatomy 0.000 description 6
- 230000003612 virological effect Effects 0.000 description 6
- 101000834898 Homo sapiens Alpha-synuclein Proteins 0.000 description 5
- 101000611936 Homo sapiens Programmed cell death protein 1 Proteins 0.000 description 5
- 101000652359 Homo sapiens Spermatogenesis-associated protein 2 Proteins 0.000 description 5
- 108010002350 Interleukin-2 Proteins 0.000 description 5
- 102000000588 Interleukin-2 Human genes 0.000 description 5
- 101100207058 Mus musculus Tmprss2 gene Proteins 0.000 description 5
- 102100036735 Prostate stem cell antigen Human genes 0.000 description 5
- 101710120463 Prostate stem cell antigen Proteins 0.000 description 5
- 230000005867 T cell response Effects 0.000 description 5
- 108091023040 Transcription factor Proteins 0.000 description 5
- 102000040945 Transcription factor Human genes 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 238000009826 distribution Methods 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- 230000008929 regeneration Effects 0.000 description 5
- 238000011069 regeneration method Methods 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 108090000369 Glutamate Carboxypeptidase II Proteins 0.000 description 4
- 101000628547 Homo sapiens Metalloreductase STEAP1 Proteins 0.000 description 4
- 102000004890 Interleukin-8 Human genes 0.000 description 4
- 108010063738 Interleukins Proteins 0.000 description 4
- 102000015696 Interleukins Human genes 0.000 description 4
- 102100026712 Metalloreductase STEAP1 Human genes 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 108010032166 TARP Proteins 0.000 description 4
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 4
- 102000002689 Toll-like receptor Human genes 0.000 description 4
- 108020000411 Toll-like receptor Proteins 0.000 description 4
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 4
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 4
- 229940030486 androgens Drugs 0.000 description 4
- 239000012636 effector Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 4
- 230000001900 immune effect Effects 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 238000002493 microarray Methods 0.000 description 4
- 238000009021 pre-vaccination Methods 0.000 description 4
- 230000000770 proinflammatory effect Effects 0.000 description 4
- 238000012163 sequencing technique Methods 0.000 description 4
- 238000002255 vaccination Methods 0.000 description 4
- 102100036301 C-C chemokine receptor type 7 Human genes 0.000 description 3
- 101000716065 Homo sapiens C-C chemokine receptor type 7 Proteins 0.000 description 3
- 108090000978 Interleukin-4 Proteins 0.000 description 3
- 101100203797 Mus musculus Spinkl gene Proteins 0.000 description 3
- 101710196623 Stimulator of interferon genes protein Proteins 0.000 description 3
- 239000006180 TBST buffer Substances 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000002596 correlated effect Effects 0.000 description 3
- 229960004397 cyclophosphamide Drugs 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 210000002216 heart Anatomy 0.000 description 3
- 239000012188 paraffin wax Substances 0.000 description 3
- 238000002203 pretreatment Methods 0.000 description 3
- 229940030749 prostate cancer vaccine Drugs 0.000 description 3
- 210000000064 prostate epithelial cell Anatomy 0.000 description 3
- 210000000952 spleen Anatomy 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000002103 transcriptional effect Effects 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 238000011870 unpaired t-test Methods 0.000 description 3
- 210000003932 urinary bladder Anatomy 0.000 description 3
- 108091005957 yellow fluorescent proteins Proteins 0.000 description 3
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 3
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 2
- 241000193449 Clostridium tetani Species 0.000 description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 2
- 101150023780 Defb50 gene Proteins 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 238000011510 Elispot assay Methods 0.000 description 2
- 238000000729 Fisher's exact test Methods 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 2
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101001045751 Homo sapiens Hepatocyte nuclear factor 1-alpha Proteins 0.000 description 2
- 101000878253 Homo sapiens Peptidyl-prolyl cis-trans isomerase FKBP5 Proteins 0.000 description 2
- 101001091365 Homo sapiens Plasma kallikrein Proteins 0.000 description 2
- 101000605534 Homo sapiens Prostate-specific antigen Proteins 0.000 description 2
- 101001001272 Homo sapiens Prostatic acid phosphatase Proteins 0.000 description 2
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 2
- 108010002586 Interleukin-7 Proteins 0.000 description 2
- 108010067902 Peptide Library Proteins 0.000 description 2
- 102100037026 Peptidyl-prolyl cis-trans isomerase FKBP5 Human genes 0.000 description 2
- 230000006044 T cell activation Effects 0.000 description 2
- 239000004098 Tetracycline Substances 0.000 description 2
- 101710120037 Toxin CcdB Proteins 0.000 description 2
- 238000001793 Wilcoxon signed-rank test Methods 0.000 description 2
- 230000005975 antitumor immune response Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 239000013256 coordination polymer Substances 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 238000010166 immunofluorescence Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 229960000714 sipuleucel-t Drugs 0.000 description 2
- 239000004575 stone Substances 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- CCEKAJIANROZEO-UHFFFAOYSA-N sulfluramid Chemical group CCNS(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F CCEKAJIANROZEO-UHFFFAOYSA-N 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 229960001603 tamoxifen Drugs 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 229930101283 tetracycline Natural products 0.000 description 2
- 235000019364 tetracycline Nutrition 0.000 description 2
- 150000003522 tetracyclines Chemical class 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 241000712461 unidentified influenza virus Species 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- QRXMUCSWCMTJGU-UHFFFAOYSA-N 5-bromo-4-chloro-3-indolyl phosphate Chemical compound C1=C(Br)C(Cl)=C2C(OP(O)(=O)O)=CNC2=C1 QRXMUCSWCMTJGU-UHFFFAOYSA-N 0.000 description 1
- 101150004974 ACP3 gene Proteins 0.000 description 1
- HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 1
- 239000012099 Alexa Fluor family Substances 0.000 description 1
- 240000003291 Armoracia rusticana Species 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 102100025142 Beta-microseminoprotein Human genes 0.000 description 1
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 1
- 240000000606 Cardamine pratensis Species 0.000 description 1
- 235000008474 Cardamine pratensis Nutrition 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 102100030751 Eomesodermin homolog Human genes 0.000 description 1
- 102100027581 Forkhead box protein P3 Human genes 0.000 description 1
- 108700012941 GNRH1 Proteins 0.000 description 1
- 229940032072 GVAX vaccine Drugs 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 1
- 108060005986 Granzyme Proteins 0.000 description 1
- 102100030385 Granzyme B Human genes 0.000 description 1
- 102100022057 Hepatocyte nuclear factor 1-alpha Human genes 0.000 description 1
- 102100028092 Homeobox protein Nkx-3.1 Human genes 0.000 description 1
- 101000576812 Homo sapiens Beta-microseminoprotein Proteins 0.000 description 1
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 1
- 101001064167 Homo sapiens Eomesodermin homolog Proteins 0.000 description 1
- 101000861452 Homo sapiens Forkhead box protein P3 Proteins 0.000 description 1
- 101000578249 Homo sapiens Homeobox protein Nkx-3.1 Proteins 0.000 description 1
- 101000917826 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-a Proteins 0.000 description 1
- 101000917824 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-b Proteins 0.000 description 1
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 1
- 101000643024 Homo sapiens Stimulator of interferon genes protein Proteins 0.000 description 1
- 101000819111 Homo sapiens Trans-acting T-cell-specific transcription factor GATA-3 Proteins 0.000 description 1
- 101000638154 Homo sapiens Transmembrane protease serine 2 Proteins 0.000 description 1
- 101000679851 Homo sapiens Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 102100029204 Low affinity immunoglobulin gamma Fc region receptor II-a Human genes 0.000 description 1
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 1
- 208000007466 Male Infertility Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 101100091494 Mus musculus Rorc gene Proteins 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 101150025129 POP1 gene Proteins 0.000 description 1
- 101150092757 POP4 gene Proteins 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108010026552 Proteome Proteins 0.000 description 1
- 238000003559 RNA-seq method Methods 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 101710205840 Ribonuclease P protein component 2 Proteins 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 102100035533 Stimulator of interferon genes protein Human genes 0.000 description 1
- 101710090983 T-cell immunoreceptor with Ig and ITIM domains Proteins 0.000 description 1
- 102100021386 Trans-acting T-cell-specific transcription factor GATA-3 Human genes 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 108060008539 Transglutaminase Proteins 0.000 description 1
- 102100031989 Transmembrane protease serine 2 Human genes 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 description 1
- 229940127174 UCHT1 Drugs 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 108010052004 acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide Proteins 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 230000006023 anti-tumor response Effects 0.000 description 1
- 239000005441 aurora Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000010205 computational analysis Methods 0.000 description 1
- 238000000205 computational method Methods 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 229960002272 degarelix Drugs 0.000 description 1
- MEUCPCLKGZSHTA-XYAYPHGZSA-N degarelix Chemical compound C([C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CC=1C=CC(NC(=O)[C@H]2NC(=O)NC(=O)C2)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(NC(N)=O)C=C1 MEUCPCLKGZSHTA-XYAYPHGZSA-N 0.000 description 1
- 230000009274 differential gene expression Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 238000009499 grossing Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- 230000008348 humoral response Effects 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 239000012133 immunoprecipitate Substances 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229940096397 interleukin-8 Drugs 0.000 description 1
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 1
- 238000010212 intracellular staining Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 229920006008 lipopolysaccharide Polymers 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 230000009437 off-target effect Effects 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 238000007427 paired t-test Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 238000007781 pre-processing Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000011471 prostatectomy Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000011472 radical prostatectomy Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 210000003289 regulatory T cell Anatomy 0.000 description 1
- 210000005084 renal tissue Anatomy 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000011218 segmentation Effects 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 229920000260 silastic Polymers 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- YEENEYXBHNNNGV-XEHWZWQGSA-M sodium;3-acetamido-5-[acetyl(methyl)amino]-2,4,6-triiodobenzoate;(2r,3r,4s,5s,6r)-2-[(2r,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound [Na+].CC(=O)N(C)C1=C(I)C(NC(C)=O)=C(I)C(C([O-])=O)=C1I.O[C@H]1[C@H](O)[C@@H](CO)O[C@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 YEENEYXBHNNNGV-XEHWZWQGSA-M 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000000528 statistical test Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 102000003601 transglutaminase Human genes 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000003656 tris buffered saline Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4611—T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/461—Cellular immunotherapy characterised by the cell type used
- A61K39/4615—Dendritic cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/462—Cellular immunotherapy characterized by the effect or the function of the cells
- A61K39/4622—Antigen presenting cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
- A61K39/464454—Enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
- A61K39/46449—Melanoma antigens
- A61K39/464492—Glycoprotein 100 [Gp100]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/4643—Vertebrate antigens
- A61K39/4644—Cancer antigens
- A61K39/464493—Prostate associated antigens e.g. Prostate stem cell antigen [PSCA]; Prostate carcinoma tumor antigen [PCTA]; Prostatic acid phosphatase [PAP]; Prostate-specific G-protein-coupled receptor [PSGR]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/46—Cellular immunotherapy
- A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
- A61K39/464838—Viral antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/7051—T-cell receptor (TcR)-CD3 complex
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/10—Transferases (2.)
- C12N9/1025—Acyltransferases (2.3)
- C12N9/104—Aminoacyltransferases (2.3.2)
- C12N9/1044—Protein-glutamine gamma-glutamyltransferase (2.3.2.13), i.e. transglutaminase or factor XIII
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y203/00—Acyltransferases (2.3)
- C12Y203/02—Aminoacyltransferases (2.3.2)
- C12Y203/02013—Protein-glutamine gamma-glutamyltransferase (2.3.2.13), i.e. transglutaminase or factor XIII
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55522—Cytokines; Lymphokines; Interferons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/80—Vaccine for a specifically defined cancer
- A61K2039/884—Vaccine for a specifically defined cancer prostate
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
Definitions
- Transglutaminase 4 belongs to the transglutaminase family of proteins. TGM4 is expressed in prostate and has been associated with male subfertility.
- the agonist is an anti- TGM4 antibody.
- the antibody is a monoclonal antibody.
- the antibody is humanized or fully-human.
- the antibody comprises a fragment of a fully functional anti-TGM4 antibody.
- the fragment is an ScFv (single chain variable fragment).
- the TGM4 agonist is further conjugated with a second antitumor reagent.
- the second anti-tumor reagent is a cytotoxic drug.
- the top panel shows the immunoprecipitation to detect antibodies against recombinant human TGM4 and PAP in the sera of indicated patients from Fig. 11C.
- Recombinant proteins were immunoprecipitated under non-denaturing conditions with human antibodies pre and post vaccination and probed with either anti-TGM4 or anti-PAP antibody in Western blot.
- Fig. 12D shows fold change on recovered recombinant proteins using patient sera post vs pre vaccination. Paired t-tests performed, p values shown.
- Unsupervised computational analysis was performed separately for unstimulated and stimulated samples.
- 10,000 cells of postgated live, single CD4+ or CD8+ T cells from each of the 10 healthy donors were randomly selected using the DownSampleV3 plugin in FlowJo.
- unsupervised clustering was performed on the expression values of the activation and functional markers separately using the FlowSOM algorithm, which uses a self-organizing map followed by hierarchical consensus metaclustering to detect cell populations. Default parameters and a predetermined number of 10 clusters were used. The median levels of the activation and functional markers across all cells per cluster were visualized in separate heatmaps.
- Fig. 12A shows the PhlP-Seq profiling of a cohort of patients with prostate adenocarcinoma treated with ADT alone or GV AX followed by ADT in a neo-adjuvant trial (NCT01696877).
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Cell Biology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Wood Science & Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- General Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Transplantation (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Developmental Biology & Embryology (AREA)
- Virology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
La présente invention concerne une méthode de traitement du cancer de la prostate par ciblage de la transglutaminase 4 (TGM4) soit seul soit en combinaison avec d'autres thérapies telles que : l'ablation des androgènes, la chimiothérapie, la radiothérapie, les agents à petites molécules ou l'immunothérapie.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US202063072854P | 2020-08-31 | 2020-08-31 | |
US63/072,854 | 2020-08-31 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2022047325A1 true WO2022047325A1 (fr) | 2022-03-03 |
Family
ID=80355774
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2021/048273 WO2022047325A1 (fr) | 2020-08-31 | 2021-08-30 | Ciblage de tmg4 pour le traitement du cancer de la prostate |
Country Status (1)
Country | Link |
---|---|
WO (1) | WO2022047325A1 (fr) |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20160213754A1 (en) * | 2013-09-20 | 2016-07-28 | Nils LANDEGREN | Transglutaminase 4 as a prostate specific autoantigen and the methods of use thereof |
US20160279214A1 (en) * | 2015-03-27 | 2016-09-29 | Immatics Biotechnologies Gmbh | Novel peptides and combination of peptides for use in immunotherapy against various tumors |
US20160304883A1 (en) * | 2013-12-30 | 2016-10-20 | Curevac Ag | Artificial nucleic acid molecules |
US20190324030A1 (en) * | 2016-06-27 | 2019-10-24 | Juno Therapeutics, Inc. | Mhc-e restricted epitopes, binding molecules and related methods and uses |
WO2020205778A1 (fr) * | 2019-03-30 | 2020-10-08 | Biontech Us Inc. | Compositions et procédés de préparation de compositions de lymphocytes t et leurs utilisations |
-
2021
- 2021-08-30 WO PCT/US2021/048273 patent/WO2022047325A1/fr active Application Filing
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20160213754A1 (en) * | 2013-09-20 | 2016-07-28 | Nils LANDEGREN | Transglutaminase 4 as a prostate specific autoantigen and the methods of use thereof |
US20160304883A1 (en) * | 2013-12-30 | 2016-10-20 | Curevac Ag | Artificial nucleic acid molecules |
US20160279214A1 (en) * | 2015-03-27 | 2016-09-29 | Immatics Biotechnologies Gmbh | Novel peptides and combination of peptides for use in immunotherapy against various tumors |
US20190324030A1 (en) * | 2016-06-27 | 2019-10-24 | Juno Therapeutics, Inc. | Mhc-e restricted epitopes, binding molecules and related methods and uses |
WO2020205778A1 (fr) * | 2019-03-30 | 2020-10-08 | Biontech Us Inc. | Compositions et procédés de préparation de compositions de lymphocytes t et leurs utilisations |
Non-Patent Citations (1)
Title |
---|
CAO ZHI, WANG YANG, LIU ZHI-YONG, ZHANG ZHEN-SHENG, REN SHAN-CHENG, YU YONG-WEI, QIAO MENG, ZHAI BEI-BEI, SUN YING-HAO: "Overexpression of transglutaminase 4 and prostate cancer progression: a potential predictor of less favourable outcomes", ASIAN JOURNAL OF ANDROLOGY, NATURE PUBLISHING GROUP, US, vol. 15, no. 6, 1 November 2013 (2013-11-01), US , pages 742 - 746, XP055912033, ISSN: 1008-682X, DOI: 10.1038/aja.2013.79 * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Mayoux et al. | Dendritic cells dictate responses to PD-L1 blockade cancer immunotherapy | |
Du et al. | Human leukocyte antigen‐G is closely associated with tumor immune escape in gastric cancer by increasing local regulatory T cells | |
Serrels et al. | Nuclear FAK controls chemokine transcription, Tregs, and evasion of anti-tumor immunity | |
Shalapour et al. | Immunosuppressive plasma cells impede T-cell-dependent immunogenic chemotherapy | |
Idorn et al. | Chemokine receptor engineering of T cells with CXCR2 improves homing towards subcutaneous human melanomas in xenograft mouse model | |
US20220226440A1 (en) | Modulation of cancer immunity with type 2 innate lymphoid cells, interleukin 33, and/or interferon induced protein 44 | |
AU2017266686B2 (en) | Markers selectively deregulated in tumor-infiltrating regulatory T cells | |
David et al. | MUC1 upregulation promotes immune resistance in tumor cells undergoing brachyury-mediated epithelial-mesenchymal transition | |
Robinson et al. | Subtype and grade-dependent spatial heterogeneity of T-cell infiltration in pediatric glioma | |
WO2018183921A1 (fr) | Méthodes et compositions de détection et de modulation d'une signature génique de résistance à l'immunothérapie d'un cancer | |
Paret et al. | CXorf61 is a target for T cell based immunotherapy of triple-negative breast cancer | |
Lopez-Bujanda et al. | TGM4: an immunogenic prostate-restricted antigen | |
Lulla et al. | The safety and clinical effects of administering a multiantigen-targeted T cell therapy to patients with multiple myeloma | |
Ohue et al. | Prolongation of overall survival in advanced lung adenocarcinoma patients with the XAGE1 (GAGED2a) antibody | |
Seed et al. | A tumor-specific mechanism of Treg enrichment mediated by the integrin αvβ8 | |
Melis et al. | The adaptive immune system promotes initiation of prostate carcinogenesis in a human c-Myc transgenic mouse model | |
Martinek et al. | Transcriptional profiling of macrophages in situ in metastatic melanoma reveals localization-dependent phenotypes and function | |
Hu et al. | IL-2 enhanced MHC class I expression in papillary thyroid cancer with Hashimoto's thyroiditis overcomes immune escape in vitro | |
Naik et al. | Cancer testis antigen PRAME: An anti‐cancer target with immunomodulatory potential | |
Han et al. | Weighting tumor-specific TCR repertoires as a classifier to stratify the immunotherapy delivery in non–small cell lung cancers | |
Brunekreeft et al. | Deep immune profiling of ovarian tumors identifies minimal MHC-I expression after neoadjuvant chemotherapy as negatively associated with T-cell-dependent outcome | |
Cheng et al. | Upregulation of the ZNF148/PTX3 axis promotes malignant transformation of dendritic cells in glioma stem‐like cells microenvironment | |
Sun et al. | Anti-tumour effect of neo-antigen-reactive T cells induced by RNA mutanome vaccine in mouse lung cancer | |
Zhao et al. | FGL2-targeting T cells exhibit antitumor effects on glioblastoma and recruit tumor-specific brain-resident memory T cells | |
WO2022047325A1 (fr) | Ciblage de tmg4 pour le traitement du cancer de la prostate |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 21862934 Country of ref document: EP Kind code of ref document: A1 |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
122 | Ep: pct application non-entry in european phase |
Ref document number: 21862934 Country of ref document: EP Kind code of ref document: A1 |