WO2018049165A1 - Immunotherapy for polyomaviruses - Google Patents

Immunotherapy for polyomaviruses Download PDF

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Publication number
WO2018049165A1
WO2018049165A1 PCT/US2017/050686 US2017050686W WO2018049165A1 WO 2018049165 A1 WO2018049165 A1 WO 2018049165A1 US 2017050686 W US2017050686 W US 2017050686W WO 2018049165 A1 WO2018049165 A1 WO 2018049165A1
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WO
WIPO (PCT)
Prior art keywords
epitopes
subject
polyomavirus
epitope
listed
Prior art date
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Ceased
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PCT/US2017/050686
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English (en)
French (fr)
Inventor
Rajiv Khanna
George Robin Ambalathingal THOMAS
Blake Tolu AFTAB
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
QIMR Berghofer Medical Research Institute
Atara Biotherapeutics Inc
Original Assignee
Queensland Institute of Medical Research QIMR
Atara Biotherapeutics Inc
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 to BR112019004102-8A priority Critical patent/BR112019004102A2/pt
Priority to AU2017322397A priority patent/AU2017322397A1/en
Priority to RU2019110269A priority patent/RU2019110269A/ru
Priority to IL265103A priority patent/IL265103B2/en
Priority to CN201780067349.9A priority patent/CN109922830A/zh
Priority to KR1020247027913A priority patent/KR20240133760A/ko
Priority to SG11201901166QA priority patent/SG11201901166QA/en
Priority to KR1020197009875A priority patent/KR102698554B1/ko
Priority to EP17849612.1A priority patent/EP3509632A4/en
Priority to US16/331,414 priority patent/US20200197439A1/en
Priority to NZ751506A priority patent/NZ751506B2/en
Priority to JP2019514037A priority patent/JP2019536429A/ja
Application filed by Queensland Institute of Medical Research QIMR, Atara Biotherapeutics Inc filed Critical Queensland Institute of Medical Research QIMR
Priority to CA3035906A priority patent/CA3035906A1/en
Priority to MX2019002566A priority patent/MX2019002566A/es
Publication of WO2018049165A1 publication Critical patent/WO2018049165A1/en
Priority to PH12019500344A priority patent/PH12019500344A1/en
Anticipated expiration legal-status Critical
Priority to JP2023000505A priority patent/JP7821133B2/ja
Priority to AU2024264673A priority patent/AU2024264673A1/en
Ceased legal-status Critical Current

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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
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • 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
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14—Blood; Artificial blood
    • A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
    • 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
    • A61K39/12—Viral antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/10—Cellular immunotherapy characterised by the cell type used
    • A61K40/11—T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/46—Viral antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • 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
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • C07K14/01—DNA viruses
    • C07K14/025—Papovaviridae, e.g. papillomavirus, polyomavirus, SV40, BK virus, JC virus
    • 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
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • C12N5/0636—T lymphocytes
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56983—Viruses
    • 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
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/515—Animal cells
    • A61K2039/5158—Antigen-pulsed cells, e.g. T-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
    • A61K2039/58—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation
    • A61K2039/585—Medicinal preparations containing antigens or antibodies raising an immune response against a target which is not the antigen used for immunisation wherein the target is cancer
    • 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
    • A61K39/12—Viral antigens
    • A61K39/295—Polyvalent viral antigens; Mixtures of viral and bacterial antigens
    • 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
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20—Cytokines; Chemokines
    • C12N2501/23—Interleukins [IL]
    • C12N2501/2321—Interleukin-21 (IL-21)
    • 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
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/998—Proteins not provided for elsewhere
    • 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
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/22011—Polyomaviridae, e.g. polyoma, SV40, JC
    • C12N2710/22034—Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/005—Assays involving biological materials from specific organisms or of a specific nature from viruses
    • G01N2333/01—DNA viruses
    • G01N2333/03—Herpetoviridae, e.g. pseudorabies virus
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • BKV and JCV viruses typically remain latent possibly in the lymphoid organs, neuronal tissue, and kidney.
  • provided herein are methods of treating or preventing cancer (e.g., a polyomavirus associated cancer, such as a BKV, JCV, or MCV associated cancer) and/or a polyomaviius (e.g., BKV, JVK, or MCV) infection in a subject comprising administering the APCs described herein to a subject.
  • cancer e.g., a polyomavirus associated cancer, such as a BKV, JCV, or MCV associated cancer
  • a polyomaviius e.g., BKV, JVK, or MCV
  • Figure 12 shows the number of CD4 and CDS cells after culture in the presence of IL-2 or IL-2 and IL-21.
  • the total number of BKV specific CD4+ T cells was reduced in the cultures grown in the presence of IL-2 and IL-21 compared to cultures grown in IL2 alone.
  • homologous refers to sequence similarity (e.g., a nucleic acid or amino acid sequence) between two regions of the same sequence strand or between regions of two different sequence strands.
  • the term “homologous” may also be used to refer to sequence similarity between two regions of the same sequence strand or between regions of two different sequence strands. For example, when an amino acid residue position in both regions is occupied by the same amino acid residue, then the regions are homologous at that position. A first region is homologous to a second region if at least one nucleotide residue position of each region is occupied by the same residue.
  • epitope ' ' means a protein determinant capable of specific binding to an antibody or TCR.
  • Epitopes usually consist of chemically active surface groupings of molecules such as amino acids or sugar side chains. Certain epitopes can be defined by a particular sequence of amino acids to which an antibody is capable of binding.
  • polynucleotide and ' ' nucleic acid are used interchangeably. They refer to a polymeric form of nucleotides of any length, either deoxyribonucleotides or ribonucleotides, or analogs thereof. Polynucleotides may have any three-dimensional structure, and may perform any function.
  • nucleotide structure may be imparted before or after assembly of the polymer.
  • a polynucleotide may be further modified, such as by conjugation with a labeling component.
  • U nucleotides are interchangeable with T nucleotides.
  • a therapeutic that "prevents" a condition refers to a compound that when administered to a statistical sample prior to the onset of the disorder or condition, reduces the occurrence of the disorder or condition in the treated sample relative to an untreated control sample, or delays the onset or reduces the severity of one or more symptoms of the disorder or condition relative to the untreated control sample.
  • Table 3 Exemplary epitope sequences from JCV/BKV hybrid epitope sequences
  • the peptides disclosed herein comprise less than 100, 90, 80, 70, 60, 50, 40, 30, 25, 20, 15 or 10 contiguous amino acids of a viral protein. In some embodiments, the peptides disclosed herein comprise two or more of the epitopes listed in Table 1, Table 2 and/or Table 3. For example, in some embodiments, the peptide disclosed herein comprises two or more of the epitopes listed in Table 1, Table 2 and or Table 3 connected by polypeptide linkers.
  • the cells are transfected with a nucleic acid encoding a peptide provided herein.
  • methods of producing antigen-presenting cells comprising pulsing a cell with the peptides described herein. Exemplary examples of producing antigen-presenting cells can be found in WO2013088114, hereby incorporated in its entirety.
  • the nucleic acid vectors or recombinant adenoviruses provided herein encode one or more epitopes listed in Tables 1, 2, and/or 3.
  • the nucleic acid vectors or recombinant adenoviruses may consist of one or more epitopes from the same table (e.g. , one or more epitopes from Table 1, one or more epitopes from Table 2, or one or more epitopes from Table 3).
  • the nucleic acid vectors or recombinant adenoviruses may consist of one or more epitopes from the same table (e.g., Table 1), and one or more epitopes from a different table (e.g., Table 2).
  • a composition e.g., a pharmaceutical composition, such as a vaccine composition
  • a peptide e.g., comprising an epitope from Table 1
  • nucleic acid e.g., nucleic acid vector, recombinant adenovirus, antibody, CTL, or an APC described herein formulated together with a pharmaceutically acceptable carrier, as well as methods of treating cancer (e.g., a polyomavirus associated cancer, such as a BKV, JVC, or MCV associated cancer) or a polyomavirus infection (e.g., a BKV, JCV, MCV, CMV, EBV, or ADV infection) using such pharmaceutical compositions.
  • the composition includes a combination of multiple (e.g., two or more) agents provided herein.
  • Conjunctive therapy includes sequential, simultaneous and separate, and/or coadministration of the active compounds in such a way that the therapeutic effects of the first agent administered have not entirely disappeared when the subsequent treatment is administered.
  • the second agent may be co-formulated with the first agent or be formulated in a separate pharmaceutical composition.
  • the epitope is detected using an ELISA assay, a western blot assay, a FACS assay, a fluorescent microscopy assay, an Edman degradation assay and/or a mass spectrometry assay (e.g., protein sequencing).
  • the presence of the BKV or JCV epitope is detected by detecting a nucleic acid encoding the BKV, MCV or JCV epitope.
  • the nucleic acid encoding the BKV, MCV or JCV epitope is detected using a nucleic acid probe, a nucleic acid amplification assay and/or a sequencing assay.
  • FIG. 1 shows that in vitro culture of T cells with BKV peptides for 14 days resulted in expansion of virus-specific T cells. In some cases, these expansions were comparable to CMV-specific T cells.
  • Figure 2 A detailed summary of the T cell assays based on in vitro expanded T cells is presented in Figure 2.
  • BKV specific T cells in compari son to the CMV specific T cells.
  • Low levels of perforin and granzyme B was also seen with BKV specific T cells.
  • BKV specific T cells could be functionally low in effector function.
  • driving the effector function of BKV specific CTLs will be the focus of my study which could help in developing an effective adoptive T cell immunotherapy.
  • Example 4 BKV-specific T cell, expansion.
  • the peptides that responded both in BKV and JCV specific T cells were further analysed for avidity using limiting dose titration assay.
  • the peptides were titrated 10 fold starting from 1 ug /ml upto a concentration of 10 "5 g /ml. These titrated peptides were then used to recall the BKV and JCV specific CTLs in standard IFN- ⁇ intracellular cytokine assay. Representative titration assay data is shown in Figure 16.

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PCT/US2017/050686 2016-09-09 2017-09-08 Immunotherapy for polyomaviruses Ceased WO2018049165A1 (en)

Priority Applications (17)

Application Number Priority Date Filing Date Title
NZ751506A NZ751506B2 (en) 2017-09-08 Immunotherapy for polyomaviruses
RU2019110269A RU2019110269A (ru) 2016-09-09 2017-09-08 Иммунотерапия полиомавирусов
IL265103A IL265103B2 (en) 2016-09-09 2017-09-08 Immune therapy for polioviruses
CN201780067349.9A CN109922830A (zh) 2016-09-09 2017-09-08 用于多瘤病毒的免疫疗法
KR1020247027913A KR20240133760A (ko) 2016-09-09 2017-09-08 폴리오마바이러스에 대한 면역요법
SG11201901166QA SG11201901166QA (en) 2016-09-09 2017-09-08 Immunotherapy for polyomaviruses
KR1020197009875A KR102698554B1 (ko) 2016-09-09 2017-09-08 폴리오마바이러스에 대한 면역요법
EP17849612.1A EP3509632A4 (en) 2016-09-09 2017-09-08 POLYOMAVIRUS IMMUNOTHERAPY
US16/331,414 US20200197439A1 (en) 2016-09-09 2017-09-08 Immunotherapy for polyomaviruses
BR112019004102-8A BR112019004102A2 (pt) 2016-09-09 2017-09-08 imunoterapia para poliomavírus
AU2017322397A AU2017322397A1 (en) 2016-09-09 2017-09-08 Immunotherapy for polyomaviruses
JP2019514037A JP2019536429A (ja) 2016-09-09 2017-09-08 ポリオーマウイルスのための免疫療法
CA3035906A CA3035906A1 (en) 2016-09-09 2017-09-08 Immunotherapy for polyomaviruses
MX2019002566A MX2019002566A (es) 2016-09-09 2017-09-08 Inmunoterapia para poliomavirus.
PH12019500344A PH12019500344A1 (en) 2016-09-09 2019-02-18 Immunotherapy for polyomaviruses
JP2023000505A JP7821133B2 (ja) 2016-09-09 2023-01-05 ポリオーマウイルスのための免疫療法
AU2024264673A AU2024264673A1 (en) 2016-09-09 2024-11-15 Immunotherapy for polyomaviruses

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US201662385456P 2016-09-09 2016-09-09
US62/385,456 2016-09-09

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EP (1) EP3509632A4 (https=)
JP (2) JP2019536429A (https=)
KR (2) KR20240133760A (https=)
CN (1) CN109922830A (https=)
AU (2) AU2017322397A1 (https=)
BR (1) BR112019004102A2 (https=)
CA (1) CA3035906A1 (https=)
IL (1) IL265103B2 (https=)
MX (1) MX2019002566A (https=)
PH (1) PH12019500344A1 (https=)
RU (1) RU2019110269A (https=)
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Cited By (3)

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Publication number Priority date Publication date Assignee Title
WO2021014213A1 (en) * 2019-07-24 2021-01-28 The Council Of The Queensland Institute Of Medical Research Immunotherapy for polyomaviruses
US20230414742A1 (en) * 2020-11-16 2023-12-28 Advaccine (Suzhou) Biopharmaceuticals Co. Ltd Novel vaccine for preventing and treating merkel cell carcinoma
EP4458419A2 (en) 2018-09-10 2024-11-06 Atara Biotherapeutics, Inc. Methods for expanding antigen-specific car-t cells, compositions and uses related thereto

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WO2021014213A1 (en) * 2019-07-24 2021-01-28 The Council Of The Queensland Institute Of Medical Research Immunotherapy for polyomaviruses
JP2022541925A (ja) * 2019-07-24 2022-09-28 ザ カウンシル オブ ザ クイーンズランド インスティテュート オブ メディカル リサーチ ポリオーマウイルスのための免疫療法
JP7844327B2 (ja) 2019-07-24 2026-04-13 ザ カウンシル オブ ザ クイーンズランド インスティテュート オブ メディカル リサーチ ポリオーマウイルスのための免疫療法
US20230414742A1 (en) * 2020-11-16 2023-12-28 Advaccine (Suzhou) Biopharmaceuticals Co. Ltd Novel vaccine for preventing and treating merkel cell carcinoma

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