WO2023128672A1 - Nouveau variant du virus de la vaccine ayant une production accrue de virus enveloppé extracellulaire - Google Patents

Nouveau variant du virus de la vaccine ayant une production accrue de virus enveloppé extracellulaire Download PDF

Info

Publication number
WO2023128672A1
WO2023128672A1 PCT/KR2022/021646 KR2022021646W WO2023128672A1 WO 2023128672 A1 WO2023128672 A1 WO 2023128672A1 KR 2022021646 W KR2022021646 W KR 2022021646W WO 2023128672 A1 WO2023128672 A1 WO 2023128672A1
Authority
WO
WIPO (PCT)
Prior art keywords
virus
vaccinia virus
cells
present
vaccinia
Prior art date
Application number
PCT/KR2022/021646
Other languages
English (en)
Korean (ko)
Inventor
손우찬
이지영
손호선
김태희
고수민
이장미
강지연
정다솜
임희선
이동현
Original Assignee
재단법인 아산사회복지재단
울산대학교 산학협력단
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from KR1020220187984A external-priority patent/KR20230101747A/ko
Application filed by 재단법인 아산사회복지재단, 울산대학교 산학협력단 filed Critical 재단법인 아산사회복지재단
Publication of WO2023128672A1 publication Critical patent/WO2023128672A1/fr

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/76—Viruses; Subviral particles; Bacteriophages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof

Definitions

  • the present invention relates to novel vaccinia virus variants with increased extravesicular virus productivity.
  • Vaccinia virus is a membranous virus with a linear DNA genome of about 190 kb and has been used as an ideal expression vector since the early 1980s. The reason for this is that it is possible to stably insert foreign DNA of 25 kb or more, and since replication is not performed in the cytoplasm, gene expression is possible without interference of the host genome, has a relatively high level of protein synthesis, and complete post-translational-modification (post-translational modification) is possible. -translational modification) occurs.
  • vaccinia virus is being actively studied for use as a recombinant vaccine or anticancer virus due to its usefulness.
  • Vaccinia virus infects and spreads to cells through four types of particles, and each type plays a different role from infection to spread based on its characteristics.
  • the four types of viral particles are intracellular mature virus (IMV), intracellular enveloped virus (IEV), cell associated virus (CEV), and extracellular enveloped virus. ; EEV).
  • IMV intracellular mature virus
  • IEV intracellular enveloped virus
  • CEV cell associated virus
  • EEV extracellular enveloped virus.
  • EEV extra-enveloped virus
  • EEV extra-enveloped virus
  • the extravesicular virus (EEV) of vaccinia virus usually has a low composition ratio of 1-2% of the total virus generated, but is responsible for systemic dissemination and has resistance to the complement-mediated immune system.
  • the extra-enveloped virus plays a biologically important role in the survival and spread of the vaccinia virus itself, such as having relatively resistance to neutralizing antibodies compared to the intracellular mature virus. Therefore, it is known that the production of extravesicular virus of vaccinia virus and the ability to form comet plaques, which are considered important for the spread of vaccinia virus from cell to cell, are related.
  • the inventors of the present invention conducted intensive research to secure a vaccinia virus that has excellent productivity of extravesicular virus (EEV), which is related to intratumoral propagation of the virus, and maintains infectivity so as to be advantageous for use as an anticancer virus vector.
  • EEV extravesicular virus
  • IHD strain ATCC VR-156
  • isolates vaccinia virus mutants that form comet plaques by repeating passage by infecting cells only with the extra-enveloped virus in the supernatant.
  • an object of the present invention is to provide a novel vaccinia virus mutant strain.
  • Another object of the present invention is to provide a method for producing a novel vaccinia virus according to the present invention.
  • the present invention provides a novel vaccinia virus deposited under accession number KCTC 15195BP, characterized by increased production of extracellular enveloped virus (EEV).
  • EEV extracellular enveloped virus
  • the vaccinia virus may be an IHD strain, but is not limited thereto.
  • the vaccinia virus is C2L, C1L, N1L, N2L, M1L, M2L, K1L, K2L, K3L, K4L, K5L, K6L, K7R, F1L, F2L, F3L, F4L, F5L,
  • One or more genes selected from the group consisting of A52R, A53R, A55R, and A56R may be deleted, but are not limited thereto.
  • the vaccinia virus may form comet plaque, but is not limited thereto.
  • the present invention comprises the steps of (a) infecting cells with vaccinia virus and culturing the infected cells;
  • step (b) infecting other cells with vaccinia virus with the supernatant of step (a), culturing the infected cells, isolating only the supernatant, and repeating step (b);
  • step (c) a method for preparing a novel vaccinia virus according to the present invention, comprising the step of isolating the vaccinia virus proliferating from the cells infected in step (b).
  • the step (b) may be repeated 2 to 20 times, but is not limited thereto.
  • the vaccinia virus may be an IHD strain, but is not limited thereto.
  • the present invention provides a pharmaceutical composition for preventing or treating cancer comprising the vaccinia virus according to the present invention as an active ingredient.
  • the vaccinia virus of the present invention increases the productivity of the extravesicular virus related to the virus propagation ability and can enhance the spread of the virus in the tumor, thereby maximizing the oncolysis potential of the vaccinia virus, thereby achieving a significantly higher anticancer effect than the conventional vaccinia virus. expected to show
  • FIG. 1 is a view showing the results of plaque assay for each passage after subculture in order to isolate a novel vaccinia virus according to an embodiment of the present invention.
  • FIGS. 2a to 5b show the results of next-generation sequencing analysis with wild-type vaccinia virus in order to verify genetic mutations of vaccinia virus according to an embodiment of the present invention
  • FIGS. 2a to 2c and 3a to 5b 3E is a result of next-generation sequencing analysis of the left arm region of a vaccinia virus isolate according to an embodiment of the present invention
  • FIGS. 4A to 4C and 5A to 5B are diagrams showing the results of next-generation sequencing analysis of the A52R to A56R gene region.
  • 2A to 2C show one figure as a whole, and each figure is positioned from left to right in one figure in the order of FIGS. 2A, 2B, and 2C.
  • Figures 3a to 3e represent one figure as a whole, and each figure is positioned from left to right in one figure in the order of Figures 3a, 3b, 3c, 3d, and 3e.
  • 4A to 4C show one figure as a whole, and each figure is positioned from left to right in one figure in the order of Figs. 4A, 4B, and 4C.
  • Figures 5a and 5b show one figure as a whole, and in one figure, Fig. 5a is located on the left and Fig. 5b is located on the right.
  • FIG. 6 is a diagram showing the results of measuring the titers of vaccinia virus and wild-type vaccinia virus according to an embodiment of the present invention.
  • the inventors of the present invention conducted intensive research to secure a vaccinia virus that has excellent productivity of extravesicular virus (EEV), which is related to intratumoral propagation of the virus, and maintains infectivity so as to be advantageous for use as an anticancer virus vector.
  • EEV extravesicular virus
  • IHD strain ATCC VR-156
  • isolates vaccinia virus mutants that form comet plaques by repeating passage by infecting cells only with the extra-enveloped virus in the supernatant.
  • the present invention provides a novel vaccinia virus mutant strain deposited under accession number KCTC 15195BP, characterized by increased production of extracellular enveloped virus (EEV).
  • EEV extracellular enveloped virus
  • novel vaccinia virus according to the present invention can be obtained through the following steps:
  • Vero cells were spread on a 6-well plate at 8 ⁇ 10 5 per well and cultured overnight . Dilute it in the medium at 10 -5 and dispense 1 mL each. After 48 hours of incubation, all the medium in each well was sampled, centrifuged at 3600 rpm for 5 minutes, and only the supernatant was separated and used as the virus to be infected in the next passage.
  • the vaccinia virus according to the present invention can be obtained by isolating the virus after finding it.
  • the vaccinia virus according to the present invention obtained through the above process is a novel virus with different genetic information from the parent virus (wild-type IHD strain vaccinia virus), which was published in KCTC (Korean Collection for Type Culture) in November 2022. It was deposited on the 15th (accession number: KCTC 15195B).
  • vaccinia virus is a large, complex enveloped virus that has a linear double-stranded DNA gene of about 190 kbp and encodes about 200 genes.
  • the role of vaccinia virus as a vaccine to eradicate smallpox is well known. After the eradication of smallpox, scientists have been studying the use of vaccinia virus as a tool to transfer genes into biological tissues (gene therapy and genetic engineering).
  • Vaccinia viruses are unique among DNA viruses because they replicate only in the cytoplasm of the host cell. Thus, a large genome is required to encode viral enzymes and proteins necessary for viral DNA replication.
  • IMV intracellular mature virus
  • IEV intracellular enveloped virus
  • CEV cell associated virus
  • EEV extracellular enveloped virus
  • the strain of the vaccinia virus may be Western Reserve, Copenhagen, Wyeth, or IHD, but is preferably an IHD strain.
  • the vaccinia virus may be natural or genetically modified. According to one embodiment of the present invention, it may preferably be ATCC's VR-156 IHD strain, but is not limited thereto.
  • the vaccinia virus is C2L, C1L, N1L, N2L, M1L, M2L, K1L, K2L, K3L, K4L, K5L, K6L, K7R, F1L, F2L, F3L, F4L, F5L, A52R, A53R,
  • One or more genes selected from the group consisting of A55R and A56R may be deleted, but are not limited thereto.
  • the vaccinia virus is the C2L, C1L, N1L, N2L, M1L, M2L, K1L, K2L, K3L, K4L, K5L, K6L, K7R, F1L, F2L, F3L, F4L, and It may be characterized by deletion of about 15 kb in the left arm region containing the F5L gene.
  • the vaccinia virus may be characterized in that A52R, A53R, A55R, and A56R gene deletions of about 3.7 kb in length from the A52R to A56R gene location occur.
  • the vaccinia virus may form a comet plaque, but is not limited thereto.
  • plaque means a comet-shaped plaque
  • the formation of comet plaque of vaccinia virus may represent the formation and propagation of an extravesicular virus that plays an important role in systemic propagation.
  • the present invention comprises the steps of (a) infecting cells with vaccinia virus and culturing the infected cells;
  • step (b) infecting other cells with vaccinia virus with the supernatant of step (a), culturing the infected cells, isolating only the supernatant, and repeating step (b);
  • step (c) isolating the proliferating vaccinia virus from the infected cells of step (b);
  • the supernatant contains the extravesicular virus of the vaccinia virus, thereby infecting the cells with the vaccinia virus.
  • step (b) another cell (second cell) distinct from the cell (first cell) of step (a) is infected with vaccinia virus with the supernatant of step (a) and cultured. Then, only the supernatant of the second cell is separated, and another cell (third cell) is infected with vaccinia virus using the supernatant separated from the second cell, cultured, and then only the supernatant of the third cell After separation, it means repeating a series of processes such as infecting and culturing another cell (fourth cell) using the supernatant separated from the third cell. That is, step (b) means subculture using the culture supernatant of vaccinia virus-infected cells.
  • cells used in the vaccinia virus production method may be cells of the same type or different types, and the cells may be animal cultured cells.
  • the animal cultured cells may be generally used animal cultured cells such as CHO cells, HEK cells, COS cells, 3T3 cells, myeloma cells, BHK cells, HeLa cells, Vero cells, etc. According to the embodiment, Vero cells, but any cell known to be used for infection or propagation of vaccinia virus may be used without limitation.
  • the step (b) is 2 to 20 times, 2 to 18 times, 2 to 16 times, 2 to 14 times, 2 to 12 times, 2 to 10 times, 2 to 10 times 8 times, 2 to 6 times, 2 to 4 times, 2 to 3 times, 3 to 18 times, 3 to 16 times, 3 to 14 times, 3 to 12 times, 3 to 10 times , 3 to 8 times, 3 to 6 times, 3 to 4 times, 4 to 5 times, 5 to 9 times, 9 to 15 times, 2 times, 3 times, 4 times, 5 times, 6 times It may be repeated 7 times, 8 times, 9 times, 10 times, 11 times, 12 times, 13 times, 14 times, or 15 times, and according to an embodiment of the present invention, the back time of step (b) There is no limit to the number of repetitions of step (b) as long as comet plaques are formed in cells infected with Nia virus.
  • the vaccinia virus may be an IHD strain, and according to an embodiment of the present invention, it may preferably be ATCC's VR-156 IHD strain, but is not limited thereto.
  • the present invention may provide a pharmaceutical composition for preventing or treating cancer comprising the vaccinia virus according to the present invention as an active ingredient.
  • the vaccinia virus is characterized in that the production of extravesicular virus (EEV), which plays an important role in systemic dissemination, is improved, and thus the efficiency of anticancer treatment can be improved by maximizing the oncolytic potential of the vaccinia virus.
  • EEV extravesicular virus
  • the novel vaccinia virus can be used for the treatment and prevention of hyperproliferative diseases such as cancer.
  • Examples contemplated for treatment include gallbladder cancer, colorectal cancer, pancreatic cancer, leukemia, ovarian cancer, stomach cancer, lung cancer, breast cancer, liver cancer, bronchial cancer, nasopharynx cancer, laryngeal cancer, skin cancer, colon cancer, cervical cancer, head and neck cancer, prostate cancer, kidney cancer, bone cancer, testicular cancer, gastrointestinal cancer, lymphoma, precancerous lesions in the lung, melanoma, sarcoma, bladder cancer, and any other cancer or tumor that can be treated.
  • the effective amount of the pharmaceutical composition is defined as sufficient to induce tumor killing or destruction or lysis of cancer cells as well as slowly inhibiting or reducing the growth of tumors or their size, and in any case eradication of tumors include
  • the route of administration of the composition of the present invention will vary depending on the location and nature of the lesion, for example intradermal, transdermal, parenteral, intravenous, intramuscular, intranasal, subcutaneous, regional (e.g. , in areas proximal to the tumor, particularly through the tumor's blood vessels or adjacent blood vessels), intratracheal, intraperitoneal, intraarterial, intravesical, intratumoral, inhalation, perfusion, lavage, and oral administration and formulation.
  • Intratumoral injection or direct injection into tumor blood vessels is particularly contemplated for isolated, accessible solid tumors.
  • Topical, regional or systemic administration may also be appropriate.
  • the volume administered will be between about 4 and 10 ml, and for tumors smaller than 4 cm, a volume of between about 1 and 3 ml will be used.
  • Multiple infusions delivered in a single dose include volumes from about 0.1 to about 0.5 ml.
  • Viral particles can advantageously be contacted via multiple infusion administration to the tumor spaced about 1 cm apart.
  • the present invention is used prior to surgery to allow for resection of inoperable tumor subjects.
  • Continuous administration may also be applied where appropriate, for example by inserting a catheter into a tumor or tumor blood vessel.
  • Such continuous perfusion can be from about 1 to 2 hours, up to about 2 to 6 hours, up to about 6 to 12 hours, up to about 12 to 24 hours, up to about 1 to 2 days, up to about 1 to 2 weeks, or Can be done over a longer period of time.
  • the dosage of the composition via continuous perfusion will be equivalent to that given via single or multiple infusions, adjusted over time while perfusion occurs.
  • limb perfusion may be used to administer the compositions of the present invention, particularly in the treatment of melanoma and sarcoma.
  • Vero African green monkey kidney epithelial cell line
  • ATCC American Type Culture Collection
  • AA antibiotic-antimycotic
  • Vaccinia virus (Vaccinia virus) and IHD strain used in this experiment were purchased from the American Type Culture Collection (ATCC, Manassas, VA, USA). The virus was propagated using Vero cells as host cells. The virus used was an infectious substance corresponding to Biosafety level 2, and the experiment was performed in a facility with appropriate safety facilities. The purchased virus was infected with 2 ⁇ 10 6 Vero cells spread on a 75T plaster, and after 48 hours, the supernatant was sampled and centrifuged to remove cell debris before use.
  • Example 3 Isolation of vaccinia virus with increased production of extracellular enveloped virus (EEV)
  • Vero cells were laid on a 6-well plate at 8 ⁇ 10 5 per well and cultured overnight. All of the medium was removed, and the vaccinia virus prepared in Example 2 was diluted in the medium at 10 0 to 10 -5 and dispensed by 1 mL. After culturing for 48 hours, the culture medium of each well was sampled, centrifuged at 3600 rpm for 5 minutes, and only the supernatant was separated and used as a virus to be infected in the next passage. This passage process was repeated 14 times. Cells sampled after 48 hours of virus infection were stained with crystal violet to confirm plaques caused by virus infection. Medium obtained from wells showing plaques that could be counted without killing all the cells in the wells was used as a virus to be infected in the next passage.
  • Crystal violet dye was prepared with 0.15% crystal violet, 8% formaldehyde, and 5% ethanol in distilled water. 1 mL of crystal violet solution was dispensed to the cells from which the medium was removed, and the cells were allowed to stand at room temperature for 5 minutes. After removing the dye by aspiration, the plate was dried to confirm the number and shape of plaques.
  • a single viral plaque was isolated through the agarose overlay method.
  • the isolated viral plaques were cultured in 10 175T flasks in large quantities and then concentrated using an ultra-high-speed centrifuge.
  • PK digestion was performed to remove non-specific protein components of the concentrated high-concentration virus sample
  • viral gDNA was extracted using a phenol/chloroform method.
  • the extracted DNA was from Macrogen Inc. (Korea)'s Whole Genome Sequencing service using the next-generation sequencing (NGS) technique was used to verify the genetic mutation of the wild-type virus and the isolated virus mutant.
  • NGS next-generation sequencing
  • Vero cells 8 ⁇ 10 5 Vero cells were seeded in a 6-well plate and cultured overnight at 37 °C, 5% CO 2 , under humid conditions, and then wild-type IHD virus and passaged virus (P14) were added to the cells at an MOI of 10. Infected and cultured for 30 minutes in a 37 ° C incubator. The virus solution was removed by aspiration, washed three times with PBS, and cultured for 24 hours by supplying 1 mL of a new medium. After 24 hours, only the supernatant was obtained and impurities were removed and used as an extracellular virus (Extra) sample.
  • Extra extracellular virus
  • Viral titers were determined by the TCID 50 assay, one of the infectivity assays. 4.2 ⁇ 10 3 Vero cells were suspended in growth medium, dispensed into each well of a 96-well plate, and incubated overnight at 37°C, 5% CO 2 , under humid conditions. A serial dilution of 1:10 of the original virus sample, for example, from 10 -2 to 10 -8 of the original virus sample was prepared, and all virus samples were vigorously vortexed until immediately before transferring 50 ⁇ l of virus to each well. The cell plate was cultured for 4 days in a 37°C, CO 2 incubator, and then CPE (Cytopathic effect) was observed.
  • CPE Cytopathic effect
  • the ratio of the virus outside the envelope of the passaged virus (P14) was higher than that of the wild-type IHD virus.
  • the vaccinia virus of the present invention increases the productivity of the extravesicular virus related to the virus propagation ability and can enhance the spread of the virus in the tumor, thereby maximizing the oncolysis potential of the vaccinia virus, thereby achieving a significantly higher anticancer effect than the conventional vaccinia virus. As can be shown, there is industrial applicability.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Zoology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Genetics & Genomics (AREA)
  • Microbiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Virology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Mycology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

La présente invention concerne un virus de la vaccine présentant une production accrue de virus enveloppé extracellulaire, et analogues. Le virus de la vaccine de la présente invention améliore la propagation intratumorale du virus en augmentant la production de virus enveloppé extracellulaire liés à la transmission virale, maximisant ainsi le potentiel oncolytique du virus de la vaccine, et devrait donc présenter un effet anticancéreux significativement élevé par comparaison avec les virus de la vaccine conventionnels.
PCT/KR2022/021646 2021-12-29 2022-12-29 Nouveau variant du virus de la vaccine ayant une production accrue de virus enveloppé extracellulaire WO2023128672A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR20210191795 2021-12-29
KR10-2021-0191795 2021-12-29
KR10-2022-0187984 2022-12-28
KR1020220187984A KR20230101747A (ko) 2021-12-29 2022-12-28 외피외 바이러스 생산이 증가한 신규한 백시니아 바이러스 변이주

Publications (1)

Publication Number Publication Date
WO2023128672A1 true WO2023128672A1 (fr) 2023-07-06

Family

ID=86999697

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2022/021646 WO2023128672A1 (fr) 2021-12-29 2022-12-29 Nouveau variant du virus de la vaccine ayant une production accrue de virus enveloppé extracellulaire

Country Status (1)

Country Link
WO (1) WO2023128672A1 (fr)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101082296B1 (ko) * 2006-06-20 2011-11-09 트랜스진 에스.에이. 폭스바이러스 및 폭스바이러스 조성물 제조 방법
US8329164B2 (en) * 2002-08-12 2012-12-11 Jennerex, Inc. Methods and compositions concerning poxviruses and cancer
KR20140112255A (ko) * 2013-03-13 2014-09-23 고려대학교 산학협력단 바이러스 생산능이 증가된 세포주 및 그 제조방법
JP2015535687A (ja) * 2012-09-28 2015-12-17 プロビオゲン アクチエンゲゼルシャフトＰｒｏＢｉｏＧｅｎ ＡＧ 新規ｍｖａウイルス及びその使用
WO2021076982A1 (fr) * 2019-10-16 2021-04-22 KaliVir Immunotherapeutics LLC Virus enveloppé extracellulaire modifié

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8329164B2 (en) * 2002-08-12 2012-12-11 Jennerex, Inc. Methods and compositions concerning poxviruses and cancer
KR101082296B1 (ko) * 2006-06-20 2011-11-09 트랜스진 에스.에이. 폭스바이러스 및 폭스바이러스 조성물 제조 방법
JP2015535687A (ja) * 2012-09-28 2015-12-17 プロビオゲン アクチエンゲゼルシャフトＰｒｏＢｉｏＧｅｎ ＡＧ 新規ｍｖａウイルス及びその使用
KR20140112255A (ko) * 2013-03-13 2014-09-23 고려대학교 산학협력단 바이러스 생산능이 증가된 세포주 및 그 제조방법
WO2021076982A1 (fr) * 2019-10-16 2021-04-22 KaliVir Immunotherapeutics LLC Virus enveloppé extracellulaire modifié

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SHCHELKUNOV S. N., YAKUBITSKIY S. N., BAUER T. V., SERGEEV A. A., KABANOV A. S., BULICHEV L. E., YURGANOVA I. A., ODNOSHEVSKIY D. : "The Influence of an Elevated Production of Extracellular Enveloped Virions of the Vaccinia Virus on Its Properties in Infected Mice", ACTA NATURAE, PARK MEDIA, RU, vol. 12, no. 4, 22 December 2020 (2020-12-22), RU , pages 120 - 132, XP093075228, ISSN: 2075-8251, DOI: 10.32607/actanaturae.10972 *

Similar Documents

Publication Publication Date Title
ES2212795T3 (es) Virus de la viruela de las aves de corral recombinante.
ES2229528T3 (es) Composicion antitumoral a base de polipetido inmunogeno de localizacion celular modificada.
JP3556666B2 (ja) 新形成の治療及び予防のための細胞障害ウイルス
US5093258A (en) Recombinant fowlpox virus and recombination vector
US20030013076A1 (en) Parapoxvirus vectors
JP7391831B2 (ja) Ｃａｒ ｔ細胞標的を発現する腫瘍溶解性ウイルス、及びその使用
IE63619B1 (en) Recombinant vaccinia virus MVA
KR20040108798A (ko) 변형 백시니아 바이러스 안카라(ｍｖａ)의 게놈내삽입부위로서의 유전자내 영역
Zhang et al. The highly attenuated oncolytic recombinant vaccinia virus GLV-1h68: comparative genomic features and the contribution of F14. 5L inactivation
WO2020239040A1 (fr) Virus oncolytique recombiné, procédé de préparation, utilisation et médicament correspondants
EP4110386A1 (fr) Vaccin à base de poxvirus recombinant contre le virus sars-cov-2
Wenske et al. Genetic reassortment of mammalian reoviruses in mice
EP3022297B1 (fr) Virus d'arn oncolytique génétiquement stable, son procédé de fabrication et utilisation associée
Taniguchi et al. Differences in plaque size and VP4 sequence found in SA11 virus clones having simian authentic VP4
WO2023128672A1 (fr) Nouveau variant du virus de la vaccine ayant une production accrue de virus enveloppé extracellulaire
RU2604187C1 (ru) РЕКОМБИНАНТНЫЙ ШТАММ VV-GMCSF-Lact ВИРУСА ОСПОВАКЦИНЫ, ОБЛАДАЮЩИЙ ОНКОЛИТИЧЕСКОЙ АКТИВНОСТЬЮ И ПРОДУЦИРУЮЩИЙ ГРАНУЛОЦИТАРНО-МАКРОФАГАЛЬНЫЙ КОЛОНИЕСТИМУЛИРУЮЩИЙ ФАКТОР ЧЕЛОВЕКА И ОНКОТОКСИЧЕСКИЙ БЕЛОК ЛАКТАПТИН
WO2019103449A2 (fr) Méthode de traitement du cancer du foie par administration d'un virus oncolytique par l'artère hépatique
Zhu et al. The attenuation of vaccinia Tian Tan strain by the removal of the viral M1L-K2L genes
Mikheeva et al. Intrinsic interference between influenza A and B viruses
WO2004087047A2 (fr) Mutants de virus de la vaccine aptes a la replication
WO2005014017A1 (fr) Composition medicinale pour traiter le cancer
US8398969B2 (en) Compositions and methods for the treatment of viral hepatitis
KR20230101747A (ko) 외피외 바이러스 생산이 증가한 신규한 백시니아 바이러스 변이주
WO2020263059A1 (fr) Virus oncolytique à sécurité et effet anticancéreux ameliorés
ES2617926T3 (es) Modulación de respuestas inmunitarias por la proteína K4 poxvírica

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: 22916813

Country of ref document: EP

Kind code of ref document: A1