BR112022011037A2 - Anticorpos ddr1 novos e usos dos mesmos - Google Patents

Anticorpos ddr1 novos e usos dos mesmos

Info

Publication number
BR112022011037A2
BR112022011037A2 BR112022011037A BR112022011037A BR112022011037A2 BR 112022011037 A2 BR112022011037 A2 BR 112022011037A2 BR 112022011037 A BR112022011037 A BR 112022011037A BR 112022011037 A BR112022011037 A BR 112022011037A BR 112022011037 A2 BR112022011037 A2 BR 112022011037A2
Authority
BR
Brazil
Prior art keywords
ddr1
antibodies
new
present disclosure
ddr1 antibodies
Prior art date
Application number
BR112022011037A
Other languages
English (en)
Portuguese (pt)
Inventor
Zhang Ningyan
An Zhiqiang
Deng Hui
Sun Xiujie
Li Rong
Original Assignee
Univ Texas
Univ George Washington
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
Application filed by Univ Texas, Univ George Washington filed Critical Univ Texas
Publication of BR112022011037A2 publication Critical patent/BR112022011037A2/pt

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2896Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2851Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the lectin superfamily, e.g. CD23, CD72
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/505Medicinal preparations containing antigens or antibodies comprising antibodies
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/50Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565Complementarity determining region [CDR]
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Zoology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Physics & Mathematics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Plant Pathology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Microbiology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
BR112022011037A 2019-12-17 2020-12-17 Anticorpos ddr1 novos e usos dos mesmos BR112022011037A2 (pt)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201962949300P 2019-12-17 2019-12-17
PCT/US2020/065618 WO2021127185A1 (en) 2019-12-17 2020-12-17 Novel ddr1 antibodies and uses thereof

Publications (1)

Publication Number Publication Date
BR112022011037A2 true BR112022011037A2 (pt) 2022-09-13

Family

ID=76478553

Family Applications (1)

Application Number Title Priority Date Filing Date
BR112022011037A BR112022011037A2 (pt) 2019-12-17 2020-12-17 Anticorpos ddr1 novos e usos dos mesmos

Country Status (10)

Country Link
US (2) US20230130372A1 (https=)
EP (1) EP4076526A4 (https=)
JP (2) JP2023508277A (https=)
CN (1) CN115443150A (https=)
AU (1) AU2020407089B2 (https=)
BR (1) BR112022011037A2 (https=)
CA (1) CA3160181A1 (https=)
IL (1) IL294019A (https=)
MX (1) MX2022007353A (https=)
WO (1) WO2021127185A1 (https=)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115443150A (zh) * 2019-12-17 2022-12-06 德克萨斯大学系统董事会 新型ddr1抗体和其用途
CN116023497B (zh) * 2022-11-09 2024-06-21 四川大学华西医院 抗ddr1抗体及其用途
AU2023379587A1 (en) * 2022-11-16 2025-06-05 Incendia Therapeutics, Inc. Methods of treating cancer using anti-ddr1 antibodies and immune checkpoint inhibitors
CN120418294A (zh) * 2022-11-16 2025-08-01 英森迪亚治疗公司 使用抗ddr1抗体治疗癌症的方法
CN118909125B (zh) * 2024-10-10 2025-01-03 杭州美赛生物医药科技有限公司 抗ddr1抗体及其应用

Family Cites Families (69)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6051397A (en) 1993-11-16 2000-04-18 Max Planck Gesellschaft Zur Forderung Der Wissenschaften DNA encoding MCK-10, a novel receptor tyrosine kinase
US20020115173A1 (en) 2000-12-11 2002-08-22 Children's Medical Center Corporation Short peptides from the 'A-region' of protein kinases which selectively modulate protein kinase activity
US7855076B2 (en) 2002-03-12 2010-12-21 The United States Of America As Represented By The Department Of Health And Human Services Use of discoidin domain receptor 1 (DDR1) and agents that affect the DDR1/collagen pathway
WO2003085125A1 (en) 2002-04-03 2003-10-16 Agy Therapeutics, Inc. Use of biomolecular targets in the treatment and visualization of brain tumors
US20070025997A1 (en) 2002-04-03 2007-02-01 Usha Nagavarapu Use of biomolecular targets in the treatment and visualization of brain tumors
US20100166731A1 (en) 2005-09-30 2010-07-01 Bartz Steven R Methods and Compositions for Treating Cancer
EP1992347A1 (en) 2007-05-18 2008-11-19 Cellzome Ag Treatment of DDR1 positive cancer using imatinib
US8652843B2 (en) 2008-08-12 2014-02-18 Oncomed Pharmaceuticals, Inc. DDR1-binding agents and methods of use thereof
CA2780221A1 (en) 2009-11-04 2011-05-12 Fabrus Llc Methods for affinity maturation-based antibody optimization
AU2011295968B2 (en) 2010-09-01 2017-01-05 Biogen Ma Inc. Rapid generation of anti-idiotypic antibodies
WO2012085064A1 (en) 2010-12-23 2012-06-28 Roche Diagnostics Gmbh Detection of a posttranslationally modified polypeptide by a bi-valent binding agent
MX2013011363A (es) * 2011-04-01 2014-04-25 Sloan Kettering Inst Cancer Anticuerpos para peptidos citosolicos.
US9550835B2 (en) * 2011-08-23 2017-01-24 Chugai Seiyaku Kabushiki Kaisha Anti-DDR1 antibody having anti-tumor activity
GB201115529D0 (en) * 2011-09-08 2011-10-26 Imp Innovations Ltd Antibodies, uses and methods
US10633451B2 (en) 2012-02-03 2020-04-28 Hoffmann-La Roche Inc. Bispecific antibody molecules with antigen-transfected T-cells and their use in medicine
HK1204926A1 (en) 2012-02-29 2015-12-11 吉联亚生物科技有限公司 Antibodies to matrix metalloproteinase 9
US11873281B2 (en) 2012-07-12 2024-01-16 Hangzhou Dac Biotech Co., Ltd. Conjugates of cell binding molecules with cytotoxic agents
US20140086913A1 (en) 2012-09-24 2014-03-27 Gilead Sciences, Inc. Anti-ddr1 antibodies
WO2014047624A1 (en) * 2012-09-24 2014-03-27 Gilead Sciences, Inc. Anti-ddr1 antibodies
WO2014140330A1 (en) 2013-03-15 2014-09-18 Oryzon Genomics, S.A. Anti-ddr1 internalizing antibodies and their medical use
KR102113310B1 (ko) 2013-09-03 2020-05-20 아주대학교 산학협력단 암 세포 분리용 조성물, 키트 및 이를 이용한 분리 방법
CN115160441A (zh) 2013-09-26 2022-10-11 埃博灵克斯股份有限公司 双特异性纳米抗体
WO2015081127A2 (en) 2013-11-26 2015-06-04 Gilead Sciences, Inc. Therapies for treating myeloproliferative disorders
US20170158762A1 (en) * 2014-01-30 2017-06-08 Anaptysbio, Inc. Antibodies directed against discoidin domain receptor family, member 1 (ddr1)
IL252192B2 (en) 2014-11-10 2024-03-01 Del Mar Pharmaceuticals Dianhydrogalactitol together with radiation to treat non-small-cell carcinoma of the lung and glioblastoma multiforme
US9694084B2 (en) 2014-12-23 2017-07-04 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
WO2016201370A1 (en) 2015-06-12 2016-12-15 Dana-Farber Cancer Institute, Inc. Combination therapy of transcription inhibitors and kinase inhibitors
AU2017228371A1 (en) 2016-03-04 2018-09-13 Gilead Sciences, Inc. Compositions and combinations of autotaxin inhibitors
KR20180007924A (ko) 2016-07-14 2018-01-24 주식회사 코리아하이텍 차량용 빔프로젝터 방열 장치
US20190310250A1 (en) * 2016-12-16 2019-10-10 Merck Patent Gmbh Methods for the use of galectin 3 binding protein detected in the urine for monitoring the severity and progression of lupus nephritis
CA3047593A1 (en) * 2017-01-02 2018-07-05 The Board Of Regents Of The University Of Texas System Anti-lair1 antibodies and their uses
CA3055256A1 (en) * 2017-03-09 2018-09-13 Mab Discovery Gmbh Antibodies specifically binding to human il-1r7
WO2018183921A1 (en) 2017-04-01 2018-10-04 The Broad Institute, Inc. Methods and compositions for detecting and modulating an immunotherapy resistance gene signature in cancer
KR20210122319A (ko) 2017-04-06 2021-10-08 항저우 디에이씨 바이오테크 씨오, 엘티디 비스-링키지를 사용한 세포독성 약물의 접합
KR20200007905A (ko) 2017-05-18 2020-01-22 리제너론 파마슈티칼스 인코포레이티드 사이클로덱스트린 단백질 약물 접합체
WO2018237287A1 (en) * 2017-06-22 2018-12-27 Apexigen, Inc. Anti-vista antibodies and methods of use
EP3655961A4 (en) 2017-07-17 2021-09-01 Massachusetts Institute of Technology HEALTHY AND SICK BARRIER TISSUE CELL ATLAS
MX2020004691A (es) 2017-11-07 2020-08-20 Regeneron Pharma Enlazadores hidrofilicos para conjugados anticuerpo-farmaco.
EP3621652A4 (en) 2017-12-31 2021-01-13 Hangzhou DAC Biotech Co, Ltd CONJUGATE OF ANALOGUE OF TUBULYSIN WITH BRANCHED LINKS
WO2019243431A1 (en) 2018-06-20 2019-12-26 INSERM (Institut National de la Santé et de la Recherche Médicale) Compositions for treating melanoma
EA202190189A1 (ru) 2018-07-05 2021-04-16 Ханчжоу Дэк Биотек Ко., Лтд Сшитое производное димера пирролобензодиазепина (pbd) и его конъюгаты
WO2020046770A1 (en) 2018-08-31 2020-03-05 Institute For Cancer Research D/B/A The Research Institute Of Fox Chase Cancer Center Kinase activity in tumors
IL282182B2 (en) 2018-10-12 2025-09-01 Hangzhou Dac Biotech Co Ltd Cytotoxic drug conjugates with a bis linkage
CN120698983A (zh) 2018-12-20 2025-09-26 C4医药公司 靶向蛋白降解
CA3128264A1 (en) 2019-01-31 2020-08-06 Hangzhou Dac Biotech Co., Ltd A conjugate of an amanita toxin with branched linkers
PH12021500050A1 (en) 2019-06-24 2022-05-02 Hangzhou Dac Biotech Co Ltd A conjugate of a cytotoxic agent to a cell binding molecule with branched linkers
CN114040781A (zh) 2019-06-24 2022-02-11 杭州多禧生物科技有限公司 Tubulysin衍生物与细胞结合分子偶联物的制剂配方
WO2021011634A1 (en) 2019-07-15 2021-01-21 Kymera Therapeutics, Inc. Protein degraders and uses thereof
KR20210053252A (ko) 2019-11-01 2021-05-11 (주)셀레메디 면역 관문 분자와 결합 가능한 분자가 융합된 단백질 및 이의 용도
WO2021086159A1 (ko) 2019-11-01 2021-05-06 (주)셀레메디 면역 관문 분자와 결합 가능한 분자가 융합된 단백질 및 이의 용도
CN115443150A (zh) * 2019-12-17 2022-12-06 德克萨斯大学系统董事会 新型ddr1抗体和其用途
AU2021225870A1 (en) 2020-02-27 2022-10-20 Janssen Biotech, Inc. Materials and methods for modulating an immune response
US20210284731A1 (en) 2020-03-13 2021-09-16 Janssen Biotech, Inc. Methods and materials for modulating an immune response
BR112022025583A2 (pt) 2020-06-19 2023-01-03 Hangzhou Dac Biotech Co Ltd Conjugado de molécula de ligação à superfície celular e análogo de camptotecina, composto conjugável, célula de tumor, composição farmacêutica, agente quimioterapêutico, e, agentes sinergísticos
CN116723839A (zh) 2020-10-14 2023-09-08 C4医药公司 用于降解靶蛋白质的三环杂双官能化合物
WO2022092974A1 (ko) 2020-10-30 2022-05-05 (주)셀레메디 항체 유사 단백질 및 그 용도
WO2022135332A1 (zh) 2020-12-21 2022-06-30 映恩生物制药(苏州)有限公司 一种甾体偶联物
CN114807042B (zh) 2021-01-22 2024-09-03 南京助天中科科技发展有限公司 一种嵌合抗原受体改造的nk细胞及其制备方法与应用
WO2022171101A1 (zh) 2021-02-10 2022-08-18 映恩生物制药(苏州)有限公司 一种甾体偶联物
NL2028075B1 (en) 2021-04-26 2022-11-03 Alphathera Ag Targeting system for cancer comprising a radioisotope
WO2022235059A1 (ko) 2021-05-03 2022-11-10 (주)셀레메디 폐암의 예방 또는 치료용 약학 조성물
JP2024524301A (ja) 2021-07-02 2024-07-05 ラエクナ セラピューティクス シャンハイ カンパニー リミテッド 活性化肝星細胞(hsc)の枯渇及びその使用
CN120463762A (zh) 2021-08-26 2025-08-12 映恩生物科技(上海)有限公司 一种甾体化合物及其缀合物
US20250179114A1 (en) 2021-09-14 2025-06-05 Duality Biologics (Suzhou) Co., Ltd. Anti-Inflammatory Compound and Use Thereof
EP4405487A4 (en) 2021-09-26 2025-12-03 Wuxi Biologics Ireland Ltd IL-2 VARIANTS AND THEIR FUSING PROTEINS
WO2023061478A1 (zh) 2021-10-15 2023-04-20 先声再明医药有限公司 三环类化合物
EP4426727A2 (en) 2021-11-03 2024-09-11 Hangzhou Dac Biotech Co., Ltd. Specific conjugation of an antibody
WO2023163873A1 (en) 2022-02-23 2023-08-31 Mayo Foundation For Medical Education And Research Synergistic drug combinations to treat cancer
JP2025507733A (ja) 2022-02-28 2025-03-21 ウーシー バイオロジクス アイルランド リミテッド Il-15変異体を含むヘテロ二量体ポリペプチド錯体とその使用

Also Published As

Publication number Publication date
US12331130B2 (en) 2025-06-17
US20230235078A1 (en) 2023-07-27
WO2021127185A1 (en) 2021-06-24
JP2024164067A (ja) 2024-11-26
JP2023508277A (ja) 2023-03-02
US20230130372A1 (en) 2023-04-27
CA3160181A1 (en) 2021-06-24
CN115443150A (zh) 2022-12-06
AU2020407089A1 (en) 2022-06-30
IL294019A (en) 2022-08-01
MX2022007353A (es) 2022-09-19
EP4076526A4 (en) 2024-07-03
EP4076526A1 (en) 2022-10-26
AU2020407089B2 (en) 2023-06-01

Similar Documents

Publication Publication Date Title
BR112022011037A2 (pt) Anticorpos ddr1 novos e usos dos mesmos
BR112021023229A2 (pt) Conjugados anticorpo-fármaco inibidores de mcl-1 e métodos de uso
BR112017025080A2 (pt) composto conjugado de fármaco com anticorpo anti-cd123, composição conjugada de fármaco com anticorpo, método de tratamento de um paciente que tem um câncer que expressa cd123, composição farmacêutica, e, anticorpo intacto ou fragmento de ligação de antígeno
BR112019000071A2 (pt) conjugados adjuvantes de anticorpo
BR112019005670A2 (pt) anticorpos anti-muc16 (mucina 16)
EA201990781A1 (ru) Анти-steap2 антитела, конъюгаты антитело-лекарственное средство и биспецифические антигенсвязывающие молекулы, которые связывают steap2 и cd3, и их применение
BR112016016207A2 (pt) Anticorpo anti-pd-l1 isolado ou fragmento de ligação ao antígeno do mesmo, seu método de produção, composição farmacêutica, molécula de polinucleotídeo isolada, vetor, célula, e uso dos mesmos
BR112017019617A2 (pt) Anticorpo, composto conjugado anticorpo- fármaco anti-cd48, composição de conjugado anticorpo-fármaco, métodos para tratar um paciente com um câncer que expressa cd48, para produzir um anticorpo anti-cd48 e para produzir um conjugado anticorpo-fármaco anti-cd48, ácido nucléico isolado, vetor isolado, e, célula hospedeira isolada
BR112015007672A2 (pt) anticorpos anti-pd-l1 monoclonais humanos e métodos de uso
JOP20220161A1 (ar) جسم مضاد لـ lilrb1 واستخداماته
MX2024007724A (es) Conjugados de farmaco-anticuerpo anti-antigeno de membrana especifico de prostata (psma) humanizado
BR112019002168A2 (pt) anticorpos trivalentes bispecíficos ligantes a claudina6 ou claudina18.2 e cd3 para o tratamento de doenças cancerígenas que expressam claudina
BR112014018481A2 (pt) anticorpo monoclonal ou policlonal ou um fragmento de ligação a antígeno do mesmo, polinucleotídeo, anticorpo monoclonal, vetor, hibridoma, anticorpo, hibridoma 5166-2 e/ou 5166-9, anticorpo ou fragmento de ligação a antígeno, composição farmacêutica, uso do anticorpo ou fragmento de ligação a anticorpo, método para tratar câncer, método para diagnosticar câncer em um indivíduo, anticorpo, método, composição ou uso
EA202091810A1 (ru) Антитела к b7-h4 и способы их применения
CY1118053T1 (el) Φαρμακευτικες συνθεσεις με ανθεκτικοτητα σε διαλυτο cea
MX2021005323A (es) Metodos de tratar la oftalmopatía de graves mediante el uso de anticuerpos anti-fcrn.
MX2021010893A (es) Anticuerpo biespecifico enlazado especificamente a vegf y ang2.
BR112018070948A2 (pt) anticorpos anti-psma e utilização dos mesmos
BR112013021350A2 (pt) anticorpo e antígeno reconhecido de células iniciadoras de tumor e o uso destes
BR112023004415A2 (pt) Moléculas terapêuticas de ligação a b7-h4
MY202157A (en) Anti-pd-l1 antibody and use thereof
JOP20210159A1 (ar) أجسام مضادة لـ pmel17 ومترافقات منها
BR112022013298A2 (pt) Anticorpos anti-tigit, anticorpos multiespecíficos que compreendem os mesmos e métodos de uso dos mesmos
BR112021021281A2 (pt) Anticorpo monoclonal que se liga especificamente ao gitr
BR112022013403A2 (pt) Anticorpos anti-tigit, anticorpos multiespecíficos que compreendem os mesmos e métodos de uso dos mesmos