ES2841274T3 - Inmunoterapia con células T específica para WT-1 - Google Patents

Inmunoterapia con células T específica para WT-1 Download PDF

Info

Publication number
ES2841274T3
ES2841274T3 ES15753531T ES15753531T ES2841274T3 ES 2841274 T3 ES2841274 T3 ES 2841274T3 ES 15753531 T ES15753531 T ES 15753531T ES 15753531 T ES15753531 T ES 15753531T ES 2841274 T3 ES2841274 T3 ES 2841274T3
Authority
ES
Spain
Prior art keywords
seq
cell
amino acid
tcr
acid sequence
Prior art date
Legal status (The legal status 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 status listed.)
Active
Application number
ES15753531T
Other languages
English (en)
Spanish (es)
Inventor
Thomas Schmitt
Philip Greenberg
Hieu Nguyen
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.)
Fred Hutchinson Cancer Center
Original Assignee
Fred Hutchinson Cancer Center
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 Fred Hutchinson Cancer Center filed Critical Fred Hutchinson Cancer Center
Application granted granted Critical
Publication of ES2841274T3 publication Critical patent/ES2841274T3/es
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503Immunoglobulin superfamily
    • C07K14/7051T-cell receptor (TcR)-CD3 complex
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/177Receptors; Cell surface antigens; Cell surface determinants
    • A61K38/1774Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/20Interleukins [IL]
    • A61K38/2013IL-2
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/20Interleukins [IL]
    • A61K38/2086IL-13 to IL-16
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00Cellular immunotherapy
    • A61K40/10Cellular immunotherapy characterised by the cell type used
    • A61K40/11T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00Cellular immunotherapy
    • A61K40/30Cellular immunotherapy characterised by the recombinant expression of specific molecules in the cells of the immune system
    • A61K40/32T-cell receptors [TCR]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00Cellular immunotherapy
    • A61K40/40Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41Vertebrate antigens
    • A61K40/42Cancer antigens
    • A61K40/4242Transcription factors, e.g. SOX or c-MYC
    • A61K40/4243Wilms tumor 1 [WT1]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/06Immunosuppressants, e.g. drugs for graft rejection
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/46Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the cancer treated
    • A61K2239/48Blood cells, e.g. leukemia or lymphoma
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Organic Chemistry (AREA)
  • Cell Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Toxicology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Hematology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Oncology (AREA)
  • Transplantation (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Virology (AREA)
ES15753531T 2014-08-04 2015-07-30 Inmunoterapia con células T específica para WT-1 Active ES2841274T3 (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201462033045P 2014-08-04 2014-08-04
US201562164783P 2015-05-21 2015-05-21
PCT/US2015/042986 WO2016022400A1 (en) 2014-08-04 2015-07-30 T cell immunotherapy specific for wt-1

Publications (1)

Publication Number Publication Date
ES2841274T3 true ES2841274T3 (es) 2021-07-07

Family

ID=53901124

Family Applications (1)

Application Number Title Priority Date Filing Date
ES15753531T Active ES2841274T3 (es) 2014-08-04 2015-07-30 Inmunoterapia con células T específica para WT-1

Country Status (7)

Country Link
US (1) US10538572B2 (enExample)
EP (1) EP3177314B1 (enExample)
JP (2) JP6712261B2 (enExample)
CN (1) CN107074970B (enExample)
CA (1) CA2956545A1 (enExample)
ES (1) ES2841274T3 (enExample)
WO (1) WO2016022400A1 (enExample)

Families Citing this family (52)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK3071593T3 (da) 2013-11-22 2019-06-11 The Board Of Trustees Of The Univ Of Illionis Modificerede humane t-celle-receptorer med høj affinitet
CA2978186A1 (en) * 2015-03-05 2016-09-09 Fred Hutchinson Cancer Research Center Immunomodulatory fusion proteins and uses thereof
US10975436B2 (en) 2016-01-05 2021-04-13 Diamir, Llc Methods of using miRNA from bodily fluids for diagnosis and monitoring of neurodevelopmental disorders
MD3440105T2 (ro) 2016-04-08 2022-09-30 Immunocore Ltd Receptori de celulă T
US10188749B2 (en) 2016-04-14 2019-01-29 Fred Hutchinson Cancer Research Center Compositions and methods to program therapeutic cells using targeted nucleic acid nanocarriers
US11332713B2 (en) 2016-11-16 2022-05-17 KSQ Therapeutics, Inc. Gene-regulating compositions and methods for improved immunotherapy
JP7685735B2 (ja) * 2016-12-02 2025-05-30 アンヘレス セラピューティクス インコーポレイテッド 合成免疫受容体およびその使用方法
JP7348063B2 (ja) 2017-01-05 2023-09-20 フレッド ハッチンソン キャンサー センター ワクチン効力を改善するためのシステム及び方法
US11603519B2 (en) * 2017-02-06 2023-03-14 National Cancer Center Japan T-cell receptor
BR112019018863A8 (pt) * 2017-03-15 2023-05-02 Hutchinson Fred Cancer Res Tcrs de alta afinidade específicos para mage-a1 e usos dos mesmos
JP2020511136A (ja) 2017-03-17 2020-04-16 フレッド ハッチンソン キャンサー リサーチ センター 免疫調節性融合タンパク質およびその使用
ES3027565T3 (en) 2017-04-24 2025-06-16 Ospedale San Raffaele Srl Tcr and peptides
NL2019156B1 (en) * 2017-06-30 2019-01-10 Academisch Ziekenhuis Leiden H O D N Leids Univ Medisch Centrum Treatment of haematological malignancies
CA3067772A1 (en) 2017-06-30 2019-01-03 Marieke GRIFFIOEN Treatment of haematological malignancies
CN107267463A (zh) * 2017-08-23 2017-10-20 安徽惠恩生物科技股份有限公司 一种针对乳腺癌的Car‑NK细胞制备方法
EP4170029A3 (en) 2017-09-19 2023-08-30 Tropic Biosciences UK Limited Modifying the specifity of plant non-coding rna molecules for silencing gene expression
BR112020006643A2 (pt) 2017-10-03 2020-09-24 Juno Therapeutics Inc moléculas de ligação específica ao hpv
CN109777778B (zh) * 2017-11-14 2023-07-18 中国科学院广州生物医药与健康研究院 一种基因改造的γδT细胞
AR114001A1 (es) 2017-12-21 2020-07-08 Hoffmann La Roche Anticuerpos que se unen a hla- a2 / wt1
DE112019000348B4 (de) * 2018-01-05 2021-10-28 Nantbio, Inc. Umprogrammierte t-zellen ähnliche nk-zellen
BR112020018620A2 (pt) 2018-03-15 2020-12-29 KSQ Therapeutics, Inc. Composições de regulação gênica e métodos para imunoterapia aprimorada
BR112020018658A2 (pt) 2018-03-15 2020-12-29 KSQ Therapeutics, Inc. Composições de regulação gênica e métodos para imu-noterapia aprimorada
DE102018108612A1 (de) 2018-03-21 2019-09-26 Immatics US, Inc. Verfahren zur erhöhung der persistenz von adoptiv infundierten t-zellen
JP7630280B2 (ja) * 2018-04-05 2025-02-17 ジュノー セラピューティクス インコーポレイテッド 組換え受容体を発現するt細胞、関連ポリヌクレオチド、および方法
AU2019249209A1 (en) * 2018-04-05 2020-10-15 Juno Therapeutics, Inc. T cell receptors and engineered cells expressing same
EP3806888B1 (en) 2018-06-12 2024-01-31 Obsidian Therapeutics, Inc. Pde5 derived regulatory constructs and methods of use in immunotherapy
CN112585162B (zh) * 2018-08-06 2025-01-28 基因医疗免疫疗法有限责任公司 Ha-1特异性t细胞受体及其用途
WO2020049496A1 (en) * 2018-09-05 2020-03-12 Glaxosmithkline Intellectual Property Development Limited T cell modification
US12440546B2 (en) 2018-10-05 2025-10-14 International Institute Of Cancer Immunology, Inc. Composition for preventing or treating benign tumor
AU2019362879A1 (en) 2018-10-16 2021-05-27 Intellia Therapeutics, Inc. Compositions and methods for immunotherapy
GB201817821D0 (en) * 2018-10-31 2018-12-19 Ospedale San Raffaele Srl TCR and peptides
JP7611844B2 (ja) 2019-03-11 2025-01-10 フレッド ハッチンソン キャンサー センター 高アビディティwt1t細胞受容体とその使用
CN111714618B (zh) * 2019-03-22 2024-07-12 香雪生命科学技术(广东)有限公司 T细胞和高亲和力pd-1融合蛋白的组合
EP3750547A1 (en) 2019-06-13 2020-12-16 Universitätsmedizin der Johannes Gutenberg-Universität Mainz Modified nk-92 cells, and therapeutic and diagnostic uses thereof
JP7737978B2 (ja) * 2019-08-20 2025-09-11 フレッド ハッチンソン キャンサー センター Wt-1に特異的なt細胞免疫療法
JP7614659B2 (ja) * 2019-12-30 2025-01-16 ブリスター イムノテック リミテッド 強化されたt細胞受容体star及びその用途
CN114106144B (zh) * 2020-08-27 2024-01-26 溧阳瑅赛生物医药有限公司 识别hla-a*02/wt1靶点的tcr及其应用
CA3201767A1 (en) 2020-12-14 2022-06-23 Thomas M. Schmitt Compositions and methods for cellular immunotherapy
WO2022223970A2 (en) * 2021-04-21 2022-10-27 Oxford University Innovation Limited Method and composition
WO2022246250A1 (en) * 2021-05-20 2022-11-24 Washington University Neuroprotective compositions and methods
CN117980326A (zh) 2021-07-14 2024-05-03 2赛文缇生物公司 与来自抗体的结合结构域融合的经工程化的t细胞受体
CN113773378B (zh) * 2021-10-14 2023-11-03 深圳大学总医院 T细胞受体及其应用
US20240390423A1 (en) * 2021-10-29 2024-11-28 Yafei Hou T cell receptor recognizing s37f mutation in ctnnb1 and its application
JP2025513801A (ja) 2022-04-08 2025-04-30 リジェネロン・ファーマシューティカルズ・インコーポレイテッド 多部位受容体及びシグナル伝達複合体
JP2025527575A (ja) 2022-08-18 2025-08-22 イミュノコア リミテッド Mage a4に特異的なt細胞受容体融合タンパク質
WO2024092265A2 (en) * 2022-10-28 2024-05-02 Memorial Sloan-Kettering Cancer Center T cell receptors targeting ewsr1-wt1 fusion protein and uses thereof
WO2024178397A2 (en) 2023-02-24 2024-08-29 Elevatebio Technologies, Inc. Modified immune effector cells and methods of use
AU2024310260A1 (en) 2023-06-29 2025-12-11 Dispatch Biotherapeutics, Inc. Synthetic cytokine receptors
WO2025240518A1 (en) 2024-05-14 2025-11-20 Dispatch Biotherapeutics, Inc. Modified lentiviral transfer plasmids
GB202406990D0 (en) * 2024-05-16 2024-07-03 Univ Oxford Innovation Ltd T cell receptors and uses thereof
WO2025245169A1 (en) 2024-05-21 2025-11-27 Fred Hutchinson Cancer Center Immunotherapy cells equipped with a collagen-targeting payload
WO2026006767A1 (en) 2024-06-28 2026-01-02 Dispatch Biotherapeutics, Inc. Tethered il-9/il-9r and related engineered cells and methods

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5283173A (en) 1990-01-24 1994-02-01 The Research Foundation Of State University Of New York System to detect protein-protein interactions
US7067318B2 (en) 1995-06-07 2006-06-27 The Regents Of The University Of Michigan Methods for transfecting T cells
GB9518220D0 (en) 1995-09-06 1995-11-08 Medical Res Council Checkpoint gene
HK1038929B (zh) 1998-07-31 2005-05-06 株式会社国际癌症免疫研究所 基於癌抑制基因wt1的产物的癌抗原
GB9823897D0 (en) 1998-11-02 1998-12-30 Imp College Innovations Ltd Immunotherapeutic methods and molecules
JP4611022B2 (ja) 2002-09-12 2011-01-12 株式会社癌免疫研究所 癌抗原ペプチド製剤
US7575925B2 (en) 2002-12-10 2009-08-18 Sunnybrook Health Sciences Centre Cell preparations comprising cells of the T cell lineage and methods of making and using them
DK2186896T3 (en) 2004-03-31 2015-12-21 Int Inst Cancer Immunology Inc Cancer antigen peptides derived from WT1
WO2006076678A2 (en) 2005-01-13 2006-07-20 The Johns Hopkins University Prostate stem cell antigen vaccines and uses thereof
EP2352756B1 (en) 2008-11-24 2012-09-19 Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH High affinity t cell receptor and use thereof
EP2258719A1 (en) 2009-05-19 2010-12-08 Max-Delbrück-Centrum für Molekulare Medizin (MDC) Multiple target T cell receptor
GB0911566D0 (en) * 2009-07-03 2009-08-12 Immunocore Ltd T cell receptors
BR122020026648B1 (pt) 2010-09-20 2021-12-07 Biontech Cell & Gene Therapies Gmbh Receptor de células t com especificidade para ny-eso-1, composição farmacêutica compreendendo o mesmo e uso do mesmo
KR20150009556A (ko) * 2012-05-03 2015-01-26 프레드 헛친슨 켄서 리서치 센터 증강된 친화성 t 세포 수용체 및 이의 제조 방법
SG11201500423TA (en) * 2012-07-27 2015-02-27 Univ Illinois Engineering t-cell receptors
WO2014118236A2 (en) * 2013-01-29 2014-08-07 Max-Delbrück-Centrum Für Moledulare Medizin (Mdc) Berlin-Buch High avidity antigen recognizing constructs

Also Published As

Publication number Publication date
CA2956545A1 (en) 2016-02-11
JP2017523784A (ja) 2017-08-24
JP6712261B2 (ja) 2020-06-24
US20160083449A1 (en) 2016-03-24
EP3177314A1 (en) 2017-06-14
US10538572B2 (en) 2020-01-21
EP3177314B1 (en) 2020-10-07
CN107074970B (zh) 2021-07-30
JP2018183175A (ja) 2018-11-22
CN107074970A (zh) 2017-08-18
WO2016022400A1 (en) 2016-02-11

Similar Documents

Publication Publication Date Title
ES2841274T3 (es) Inmunoterapia con células T específica para WT-1
US11026969B2 (en) High affinity T cell receptors and uses thereof
JP6612963B2 (ja) 腫瘍抗原を直接認識するために組換えt細胞レセプターを使用するための組成物及び方法
ES2897731T3 (es) Composiciones y métodos para reforzar la eficacia de la inmunoterapia celular adoptiva
ES2870174T3 (es) Proteínas de fusión PD-1-CD28 y su uso en medicina
ES2904301T3 (es) Receptores de células T dirigidos contra Bob1 y usos de los mismos
ES2871400T3 (es) Células inmunitarias deficientes en SUV39H1
KR20220042161A (ko) Suv39h1에 결함이 있는 면역 세포
US20210340201A1 (en) Immunotherapy targeting kras or her2 antigens
WO2019055862A1 (en) HIGH AFFINITY T CELL RECEPTORS AND USES THEREOF
CN110857319A (zh) 一种分离的t细胞受体、其修饰的细胞、编码核酸及其应用
US20220267403A1 (en) Binding proteins specific for 5t4 and uses thereof
KR20230148837A (ko) Ror1 표적화 키메라 항원 수용체
US20230303974A1 (en) Immune Cells Defective for SOCS1
US20220009992A1 (en) T cell receptors specific for mesothelin and their use in immunotherapy
WO2023126458A1 (en) Immune cells with inactivated suv39h1 and modified tcr
EP4353252A1 (en) Antigen-specific t cells by gene editing of cd3 epsilon
CN117412985A (zh) 靶向ror1的嵌合抗原受体
CN119894923A (zh) 包含tmigd2共刺激结构域的嵌合抗原受体及其相关使用方法
Nicholson Enhancing the efficacy of TCR gene therapy