LBPO.CL04 · 临床研究 · Late-Breaking
以外周血作为癌症新抗原和反应性T细胞发现的唯一来源
Peripheral blood as the sole source for cancer neoantigen and reactive T cell discovery
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
针对新抗原的T细胞疗法需要侵入性肿瘤活检来鉴定新抗原和反应性T细胞，这限制了其适用性并可能低估肿瘤异质性。我们提出一种仅依赖外周血的新策略，通过游离DNA全外显子组测序鉴定非同义突变，并基于PD-1和CD39的共表达分离新抗原特异性CD4+和CD8+ T细胞。在初始队列的8例转移性癌症患者中，我们的方法成功鉴定了大多数新抗原，并增加了标准活检技术所检测到的T细胞反应性数量。至关重要的是，我们的方法发现了肿瘤活检分析所遗漏的额外新抗原，凸显了利用液体活检进行更广泛新抗原靶向的潜力。对更大规模的69例转移性癌症患者队列的分析显示，约半数患者可能适合我们的纯血液方法。这项概念验证研究证明了利用外周血作为肿瘤活检的替代或补充，以针对更广谱新抗原开发新抗原反应性T细胞疗法的潜力。
查看英文原文 English abstract
Neoantigen-targeted T-cell therapies require invasive tumor biopsies to identify neoantigens and reactive T cells, limiting their applicability and potentially underestimating tumor heterogeneity. We propose a novel strategy relying solely on peripheral blood to identify non-synonymous mutations via cell-free DNA whole-exome sequencing and isolate neoantigen-specific CD4 + and CD8 + T cells based on PD-1 and CD39 co-expression. Our method successfully identified most neoantigens and increased the number of T-cell reactivities detected by standard biopsy-based techniques in an initial cohort of eight metastatic cancer patients. Critically, our approach uncovered additional neoantigens missed by tumor biopsy analysis, highlighting the potential for broader neoantigen targeting using liquid biopsies. Analysis of a larger cohort of 69 metastatic cancer patients revealed that approximately half could be eligible for our blood-only approach. This proof-of-concept study demonstrates the potential of using peripheral blood as a surrogate or complement for tumor biopsies to develop neoantigen-reactive T-cell therapies against a broader spectrum of neoantigens.
利益披露 Disclosure
A. Garcia Garijo, None..
I. Creus-González, None..
P. Levy, None..
A. B. Moreno-Cárdenas, None..
M. Lozano-Rabella, None..
C. A. Fajardo, None..
R. Pujol-Borrell, None..
A. Marín, None..
J. Kusnick, None..
J. Gartner, None..
A. Yuste-Estevanez, None..
A. Calahorro, None.
J. Fernandez,
AstraZeneca Employment.
R. Sanz, None..
T. B. K. Watkins, None..
V. Galvao, None.
E. Muñoz-Couselo,
BMS; MSD; Novartis; Pierre Fabre; Regeneron; Sanofi Other, Personal fees.
MSD; Sanofi; BMS ).
J. Ros,
Sanofi Other, Speaker honoraria.
Pfizer Other, Speaker honoraria.
Takeda Other, Speaker honoraria.
Amgen Travel, Other, Speaker honoraria.
Pierre-Fabre Travel.
Servier Travel.
Merck Travel.
E. Elez,
Abbvie Deutschland Gmbh & Co KG; Agenus; Amgen Inc.; AstraZeneca Pharmaceuticals LP; Array Biopharma Inc; Bayer Pharma AG; BeiGene; Bioncotech; Therapeutics; S.L.; Biontech Rna Pharmacuticals GMBH ).
Boehringer Ingelheim; Bristol-Myers Squibb International Corporation; Celgene International SARL; Daiichi Sankyo;Inc; Debiopharm International SA; Enterome BioScience SA; Exelixis; Genentech Inc ).
Gercor; GSK; HalioDX SAS; Hoffmann-La Roche Ltd; Hutchinson Medipharma Limited; Hutchison MediPharma; International; Iovance Biotherapeutics; Janssen Research & Development; Janssen-Cilag SA ).
MedImmune; Menarini; Menarini Ricerche SPA; Merck Health KGAA; Merus NV; Mirati; Nouscom SRL.; Novartis Farmacéutica SA; Pfizer; NuCana plc.; PharmaMar SA; Pledpharma AB; Redx Pharma PLC ).
Sanofi Aventis Recherche & Développement; Scandion Oncology; Seattle Genetics Inc.; Servier; Sotio A.S.; Taiho Pharma USA Inc; Wntresearch AB ).
Agenus; Amgen; Bayer; Boehringer Ingelheim; Bristol Myers Squibb; Cure Teq AG; GlaxoSmithKline; Hoffman La – Roche; Janssen; Johnson&Johnson; Lilly; Medscape; Merck Serono, MSD; Nordic Group BV Other, Personal fees.
Novartis; Organon; Pfizer; Pierre Fabre; Repare Therapeutics Inc.; RIN Institute Inc.; Rottapharm Biotech; Sanofi; Seagen International GmbH; Servier Other, Personal fees.
Takeda Other, Personal fees.
M. Oliveira,
AstraZeneca; Daiichi-Sankyo/AstraZeneca; Gilead; iTEOS; Lilly; MSD; Pierre-Fabre; Relay Therapeutics; Eisai; Gilead; Libbs; Novartis; Pfizer; Roche; Seagen; AstraZeneca Taiwan Limited Other, personal fees.
AstraZeneca ), Travel.
Gilead ), Travel.
Eisai; Pierre-Fabre Travel.
Ayala Pharmaceuticals; Boehringer-Ingelheim; Genentech; GSK; Novartis; Roche; Seagen; Zenith Epigenetics ).
C. Saura,
AstraZeneca; Daiichi Sankyo; Eisai Europe; Ltd.; Gilead; Novartis; Pharmalex; Pfizer Inc; Phillips Health Works; Pierre Fabre; PintPharma; Puma Biotechnology Inc; Lilly; Roche Farma; SA; Seagen Int.; Other, Personal fees.
Solti; Synthon Biopharmaceuticals; Zymeworks Other, Personal fees.
AX'Consulting; AX's Consulting SARL; AstraZeneca; Boehringer Ingelheim; Brístol Meyers Squibb; Byondis BV; Daiichi Sankyo; Eisai; Exeter Pharma; F. Hoffmann - La Roche Ltda; Genentech ).
Lilly; MediTech; Merck Sharp & Döhme; Merus; Milenio; Novartis; Pfizer; Philips; Pierre Fabre; Pintafarma; Puma; RocheFarma; SACE Medhealth SL; Sanofi; Sanofi Aventis; Seagen ).
Simon Kucher & Partners SL; Solti; Biofarmacéuticos Synthon; Zymeworks ).
I. Braña,
AstraZeneca; Bicycle Therapeutics; Celgene; Dragonfly; GlaxoSmithKline; Gliknik; ISA Pharmaceuticals; Janssen Pharmaceuticals; Kura; Nanobiotics; Novartis; Northern Biologics; Orion Pharma ).
Odonate Therapeutics; Regeneron; Pfizer; Sanofi; Pharmamar; Seattle Genetics; Shattuck Labs; VCN Biosciences ).
Boehringer Ingelheim; Bristol-Myers Squibb; Immutep; Merck Serono; Merck Sharp & Dohme ), Personal fees.
Achilles Therapeutics; Cancer Expert Now; eTheRNA Immunotherapies; PCI Biotech; Pierre Fabre Other, Personal fees.
A. Oaknin, None.
R. Alemany,
Theriva Biologics Stock, ), Other, Honoraria.
J. Tabernero,
Accent Therapeutics; Alentis Therapeutics; AstraZeneca; Boehringer Ingelheim; Bristol Myers Squibb; Carina Biotech; Cartography Biosciences, Chugai; Daiichi Sankyo; F.Hoffmann-La Roche; Genentech personal fees
.
Johnson & Johnson/Janssen; Lilly; Menarini; Merus; MSD; Novartis; Ono Pharma USA; Peptomyc; Pfizer; Pierre Fabre; Quantro Therapeutics; Scandion Oncology; Scorpion Therapeutics; Servier Other, personal fees.
Sotio Biotech; Taiho; Takeda Oncology; Tolremo Therapeutics Other, Personal fees.
Alentis Therapeutics; Oniria Therapeutics; 1TRIALSP; Pangaea Oncology Stock.
R. Perez-Lopez,
AstraZeneca ).
Roche Farma S.A. ).
A. M. Frankell, None.
E. Garralda,
Novartis; Roche; Thermo Fisher; AstraZeneca; Taiho; BeiGene ).
Roche/Genentech; F. Hoffmann-La Roche; Ellipses Pharma; Neomed Therapeutics1 Inc.; Boehringer Ingelheim; Janssen Global Services; Seattle Genetics Other, Personal fees.
TFS; Alkermes; Thermo Fisher; Bristol-Myers Squibb; MabDiscovery; Anaveon; F-Star Therapeutics; Hengrui; Sanofi; Merck Sharp & Dohme; Lilly Other, Personal fees.
Novartis; Agios Pharmaceuticals; Amgen; Bayer; BeiGene USA; Blueprint Medicines; BMS; Cellestia Biotech; Debiopharm; Forma Therapeutics Other, Personal fees.
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Nanobiotix; S.A; Novartis Farmaceutica; S.A.; Pfizer; SLU; PharmaMar; S.A.U.; Pierre Fabre Medicament; Principia Biopharma Inc.; Psioxus Therapeutics Ltd.; Sanofi; Sierra Oncology; Sotio A.S. Other, Personal fees.
Symphogen A.S. Other, Personal fees.
R. D. Toledo,
AstraZeneca ).
BeiGene Pharmaceuticals ).
Novartis ).
A. Gros,
Achilles Therapeutics Other, personal fees.
Singula Bio Other, Personal fees.
BioNTech Other, Personal fees.
Instil Bio Other, Personal fees.
Pact Pharma Other, Personal fees.
Roche ), Other, Personal fees.
Merck ).
Intima Bioscience Inc.; Intellia Therapeutics, Inc.; Tailored Therapeutics; LLC; Cellular Biomedicine Group, Inc.; Geneius Biotechnology, Inc. Patent.