WO2013154760A1 - Chimeric antigen receptors targeting b-cell maturation antigen - Google Patents
Chimeric antigen receptors targeting b-cell maturation antigen Download PDFInfo
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- WO2013154760A1 WO2013154760A1 PCT/US2013/032029 US2013032029W WO2013154760A1 WO 2013154760 A1 WO2013154760 A1 WO 2013154760A1 US 2013032029 W US2013032029 W US 2013032029W WO 2013154760 A1 WO2013154760 A1 WO 2013154760A1
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- Prior art keywords
- cells
- car
- bcma
- cell
- multiple myeloma
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- 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
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- 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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- 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
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- 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
- C07K14/70517—CD8
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- 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
- C07K14/70521—CD28, CD152
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- 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
- C07K14/70578—NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
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- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/62—DNA sequences coding for fusion proteins
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- 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
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- C07—ORGANIC CHEMISTRY
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
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- C07—ORGANIC CHEMISTRY
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- C07K2319/00—Fusion polypeptide
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- 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
- FIGS 7C and 7D are graphs which depict experimental data illustrating that T- cells from Donor A expressing the anti-bcma2 CAR specifically killed the multiple myeloma cell lines H929 ( Figure 6C) and RPMI8226 ( Figure 6D) in a four-hour cytotoxicity assay at various effectontarget cell ratios.
- T-cells transduced with the negative control SP6 CAR induced much lower levels of cytotoxicity at all effectontarget ratios.
- the cytotoxicity was determined in duplicate, and the results are displayed as the mean +/- the standard error of the mean.
- T-cells expressing CARs the ability to recognize an antigen independent of antigen processing, thus bypassing a major mechanism of tumor escape.
- CARs when expressed in T-cells, CARs advantageously do not dimerize with endogenous T-cell receptor (TCR) alpha and beta chains.
- the inventive nucleic acid sequence encodes a CAR which comprises, from 5' to 3', a human CD8a signal sequence, an anti-BCMA scFv, the hinge and transmembrane regions of the human CD8a molecule, the cytoplasmic T-cell signaling domain of the human 4- IBB molecule and/or the cytoplasmic T-cell signaling domain of the human OX40 molecule, and T-cell signaling domain of the human CD3 ⁇ molecule.
- the inventive nucleic acid sequence comprises or consists of the nucleic acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3.
- the composition desirably comprises the host cells expressing the inventive nucleic acid sequence encoding a CAR, or a vector comprising the inventive nucleic acid sequence, in an amount that is effective to treat or prevent multiple myeloma or Hodgkin's lymphoma.
- treatment refers to obtaining a desired pharmacologic and/or physiologic effect.
- the effect is therapeutic, i.e., the effect partially or completely cures a disease and/or adverse symptom attributable to the disease.
- inventive CAR- encoding nucleic acid sequence can be modified in any number of ways, such that the therapeutic or prophylactic efficacy of the CAR is increased through the modification.
- the CAR can be conjugated either directly or indirectly through a linker to a targeting moiety.
- the practice of conjugating compounds, e.g., the CAR, to targeting moieties is known in the art. See, for instance, Wadwa et al., J. Drug Targeting 3 : 1 1 1 (1995), and U.S. Patent 5,087,616.
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- Health & Medical Sciences (AREA)
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Abstract
Description
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Priority Applications (44)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
NZ700362A NZ700362A (en) | 2012-04-11 | 2013-03-15 | Chimeric antigen receptors targeting b-cell maturation antigen |
KR1020147031520A KR102086874B1 (en) | 2012-04-11 | 2013-03-15 | Chimeric antigen receptors targeting b-cell maturation antigen |
CA2869562A CA2869562C (en) | 2012-04-11 | 2013-03-15 | Chimeric antigen receptors targeting b-cell maturation antigen |
EP19216091.9A EP3689383A1 (en) | 2012-04-11 | 2013-03-15 | Chimeric antigen receptors targeting b-cell maturation antigen |
MX2018008352A MX2018008352A (en) | 2012-04-11 | 2013-03-15 | Chimeric antigen receptors targeting b-cell maturation antigen. |
EA201491837A EA033110B1 (en) | 2012-04-11 | 2013-03-15 | Chimeric antigen receptor targeting b-cell maturation antigen, nucleic acid encoding same, corresponding expression vector, host cell, uses and methods |
SG11201406414WA SG11201406414WA (en) | 2012-04-11 | 2013-03-15 | Chimeric antigen receptors targeting b-cell maturation antigen |
US14/389,677 US9765342B2 (en) | 2012-04-11 | 2013-03-15 | Chimeric antigen receptors targeting B-cell maturation antigen |
KR1020207006131A KR102229945B1 (en) | 2012-04-11 | 2013-03-15 | Chimeric antigen receptors targeting b-cell maturation antigen |
JP2015505765A JP6359520B2 (en) | 2012-04-11 | 2013-03-15 | Chimeric antigen receptor targeting B cell maturation antigen |
KR1020217007607A KR20210032014A (en) | 2012-04-11 | 2013-03-15 | Chimeric antigen receptors targeting b-cell maturation antigen |
EP13714125.5A EP2836239A1 (en) | 2012-04-11 | 2013-03-15 | Chimeric antigen receptors targeting b-cell maturation antigen |
KR1020227005825A KR20220029757A (en) | 2012-04-11 | 2013-03-15 | Chimeric antigen receptors targeting b-cell maturation antigen |
AU2013246443A AU2013246443B2 (en) | 2012-04-11 | 2013-03-15 | Chimeric antigen receptors targeting B-cell maturation antigen |
BR112014024893A BR112014024893B8 (en) | 2012-04-11 | 2013-03-15 | ISOLATED OR PURIFIED NUCLEIC ACID SEQUENCE ENCODING A CHIMERIC ANTIGEN RECEPTOR (CAR) AND ITS USE, ISOLATED OR PURIFIED CARS, VECTORS, METHODS TO DESTROY CANCER CELLS AND POLYNUCLEOTIDE |
RU2014144143A RU2650805C2 (en) | 2012-04-11 | 2013-03-15 | Chimeric antigen receptors targeting b-cell maturation antigen |
CN201380027676.3A CN104379179A (en) | 2012-04-11 | 2013-03-15 | Chimeric antigen receptors targeting b-cell maturation antigen |
MX2014012222A MX357823B (en) | 2012-04-11 | 2013-03-15 | Chimeric antigen receptors targeting b-cell maturation antigen. |
IL234870A IL234870B (en) | 2012-04-11 | 2014-09-29 | Chimeric antigen receptors targeting b-cell maturation antigen |
HK15104056.6A HK1203393A1 (en) | 2012-04-11 | 2015-04-27 | Chimeric antigen receptors targeting -cell maturation antigen |
AU2017208279A AU2017208279B2 (en) | 2012-04-11 | 2017-07-26 | Chimeric antigen receptors targeting b-cell maturation antigen |
US15/692,473 US10767184B2 (en) | 2012-04-11 | 2017-08-31 | Chimeric antigen receptors targeting B-cell maturation antigen |
IL263417A IL263417B (en) | 2012-04-11 | 2018-12-02 | Chimeric antigen receptors targeting b-cell maturation antigen |
AU2019203042A AU2019203042B2 (en) | 2012-04-11 | 2019-04-30 | Chimeric antigen receptors targeting B-cell maturation antigen |
US16/683,625 US10815488B2 (en) | 2012-04-11 | 2019-11-14 | Chimeric antigen receptors targeting B-cell maturation antigen |
US16/683,543 US10876123B2 (en) | 2012-04-11 | 2019-11-14 | Chimeric antigen receptors targeting B-cell maturation antigen |
US16/683,417 US10815487B2 (en) | 2012-04-11 | 2019-11-14 | Chimeric antigen receptors targeting B-cell maturation antigen |
US16/683,435 US10738312B2 (en) | 2012-04-11 | 2019-11-14 | Chimeric antigen receptors targeting B-cell maturation antigen |
US16/683,524 US10900042B2 (en) | 2012-04-11 | 2019-11-14 | Chimeric antigen receptors targeting B-cell maturation antigen |
US16/683,453 US10738313B2 (en) | 2012-04-11 | 2019-11-14 | Chimeric antigen receptors targeting B-cell maturation antigen |
US16/683,494 US10829767B2 (en) | 2012-04-11 | 2019-11-14 | Chimeric antigen receptors targeting B-cell maturation antigen |
US16/683,477 US10844387B2 (en) | 2012-04-11 | 2019-11-14 | Chimeric antigen receptors targeting B-cell maturation antigen |
US16/684,978 US10837019B2 (en) | 2012-04-11 | 2019-11-15 | Chimeric antigen receptors targeting B-cell maturation antigen |
US16/684,994 US10829769B2 (en) | 2012-04-11 | 2019-11-15 | Chimeric antigen receptors targeting b-cell maturation antigen |
US16/684,962 US10829768B2 (en) | 2012-04-11 | 2019-11-15 | Chimeric antigen receptors targeting B-cell maturation antigen |
IL278003A IL278003A (en) | 2012-04-11 | 2020-10-13 | Chimeric antigen receptors targeting b-cell maturation antigen |
US17/117,335 US11377660B2 (en) | 2012-04-11 | 2020-12-10 | Chimeric antigen receptors targeting B-cell maturation antigen |
US17/117,368 US11359204B2 (en) | 2012-04-11 | 2020-12-10 | Chimeric antigen receptors targeting B-cell maturation antigen |
US17/117,311 US11066674B2 (en) | 2012-04-11 | 2020-12-10 | Chimeric antigen receptors targeting b-cell maturation antigen |
AU2021202158A AU2021202158A1 (en) | 2012-04-11 | 2021-04-08 | Chimeric antigen receptors targeting B-cell maturation antigen |
IL290471A IL290471A (en) | 2012-04-11 | 2022-02-09 | Chimeric antigen receptors targeting b-cell maturation antigen |
US17/745,067 US20230002776A1 (en) | 2012-04-11 | 2022-05-16 | Chimeric antigen receptors targeting b-cell maturation antigen |
US17/938,529 US11773396B2 (en) | 2012-04-11 | 2022-10-06 | Chimeric antigen receptors targeting B-cell maturation antigen |
US17/938,535 US11827889B2 (en) | 2012-04-11 | 2022-10-06 | Chimeric antigen receptors targeting B-cell maturation antigen |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201261622600P | 2012-04-11 | 2012-04-11 | |
US61/622,600 | 2012-04-11 |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
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US14/389,677 A-371-Of-International US9765342B2 (en) | 2012-04-11 | 2013-03-15 | Chimeric antigen receptors targeting B-cell maturation antigen |
US15/692,473 Continuation US10767184B2 (en) | 2012-04-11 | 2017-08-31 | Chimeric antigen receptors targeting B-cell maturation antigen |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2013154760A1 true WO2013154760A1 (en) | 2013-10-17 |
Family
ID=48045750
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2013/032029 WO2013154760A1 (en) | 2012-04-11 | 2013-03-15 | Chimeric antigen receptors targeting b-cell maturation antigen |
Country Status (17)
Country | Link |
---|---|
US (19) | US9765342B2 (en) |
EP (2) | EP3689383A1 (en) |
JP (5) | JP6359520B2 (en) |
KR (4) | KR20210032014A (en) |
CN (3) | CN110295186A (en) |
AU (4) | AU2013246443B2 (en) |
BR (1) | BR112014024893B8 (en) |
CA (1) | CA2869562C (en) |
EA (2) | EA033110B1 (en) |
HK (1) | HK1203393A1 (en) |
IL (4) | IL234870B (en) |
IS (1) | IS9056A (en) |
MX (3) | MX2018008352A (en) |
NZ (1) | NZ700362A (en) |
RU (2) | RU2766608C2 (en) |
SG (1) | SG11201406414WA (en) |
WO (1) | WO2013154760A1 (en) |
Cited By (138)
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WO2014122143A1 (en) | 2013-02-05 | 2014-08-14 | Engmab Ag | Method for the selection of antibodies against bcma |
WO2015052538A1 (en) * | 2013-10-10 | 2015-04-16 | Ucl Business Plc | Chimeric antigen receptor |
WO2015123527A1 (en) * | 2014-02-14 | 2015-08-20 | Bellicum Pharmaceuticals, Inc. | Methods for activating t cells using an inducible chimeric polypeptide |
WO2015157432A1 (en) * | 2014-04-10 | 2015-10-15 | Seattle Children's Hospital (dba Seattle Children's Research Institute) | Drug related transgene expression |
WO2015158671A1 (en) * | 2014-04-14 | 2015-10-22 | Cellectis | Bcma (cd269) specific chimeric antigen receptors for cancer immunotherapy |
WO2015188119A1 (en) * | 2014-06-06 | 2015-12-10 | Bluebird Bio, Inc. | Improved t cell compositions |
WO2015187528A1 (en) * | 2014-06-02 | 2015-12-10 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Chimeric antigen receptors targeting cd-19 |
WO2016007827A1 (en) * | 2014-07-11 | 2016-01-14 | Anthrogenesis Corporation | Methods of improving vector transduction efficiency into t lymphocytes |
EP2982694A1 (en) | 2014-08-04 | 2016-02-10 | EngMab AG | Bispecific antibodies against cd3epsilon and bcma |
US20160046724A1 (en) * | 2014-07-21 | 2016-02-18 | The Trustees Of The University Of Pennsylvania | Treatment of cancer using humanized anti-bcma chimeric antigen receptor |
WO2016014789A3 (en) * | 2014-07-24 | 2016-03-17 | Bluebird Bio, Inc. | Bcma chimeric antigen receptors |
EP3023437A1 (en) | 2014-11-20 | 2016-05-25 | EngMab AG | Bispecific antibodies against CD3epsilon and BCMA |
EP3029068A1 (en) | 2014-12-03 | 2016-06-08 | EngMab AG | Bispecific antibodies against CD3epsilon and BCMA for use in the treatment of diseases |
WO2016090320A1 (en) | 2014-12-05 | 2016-06-09 | Memorial Sloan-Kettering Cancer Center | Chimeric antigen receptors targeting b-cell maturation antigen and uses thereof |
WO2016120216A1 (en) * | 2015-01-26 | 2016-08-04 | Cellectis | mAb-DRIVEN CHIMERIC ANTIGEN RECEPTOR SYSTEMS FOR SORTING/DEPLETING ENGINEERED IMMUNE CELLS |
WO2016100985A3 (en) * | 2014-12-19 | 2016-08-18 | Dana-Farber Cancer Institute, Inc. | Chimeric antigen receptors and methods of use thereof |
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WO2016166630A1 (en) * | 2015-04-13 | 2016-10-20 | Pfizer Inc. | Chimeric antigen receptors targeting b-cell maturation antigen |
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US20170166622A1 (en) * | 2015-05-18 | 2017-06-15 | TCR2 Therapeutics Inc. | Compositions and methods for tcr reprogramming using fusion proteins |
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CN107074929A (en) * | 2014-05-02 | 2017-08-18 | 宾夕法尼亚大学董事会 | The composition and method of chimeric autoantibody recipient T cells |
WO2017211900A1 (en) | 2016-06-07 | 2017-12-14 | Max-Delbrück-Centrum für Molekulare Medizin | Chimeric antigen receptor and car-t cells that bind bcma |
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US10125193B2 (en) | 2014-02-14 | 2018-11-13 | Board Of Regents, The University Of Texas System | Chimeric antigen receptors and methods of making |
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