LBPO.CL04 · 临床研究 · Late-Breaking

Peripheral blood as the sole source for cancer neoantigen and reactive T cell discovery

编号 LB413 展板 3 时间 4/22 09:00–12:00 区域 Section 51 主讲 Andrea Garcia Garijo, PhD

分会场 Late-Breaking Research: Clinical Research 4

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作者与单位

Andrea Garcia Garijo¹, Immaculada Creus-González¹, Pierre Levy¹, Ana Belen Moreno-Cárdenas¹, Maria Lozano-Rabella¹, Carlos Alberto Fajardo¹, Ricardo Pujol-Borrell¹, Albert Marín¹, Johanna Kusnick¹, Jared Gartner², Anna Yuste-Estevanez¹, Alma Calahorro¹, Jose Fernandez¹, Rebeca Sanz³, Thomas B. K. Watkins⁴, Vladimir Galvao¹, Eva Muñoz-Couselo¹, Javier Ros¹, Elena Elez¹, Mafalfa Oliveira¹, Cristina Saura¹, Irene Braña¹, Ana Oaknin¹, Ramon Alemany³, Josep Tabernero¹, Raquel Perez-Lopez¹, Alexander M. Frankell⁵, Elena Garralda¹, Rodrigo De Almeida Toledo¹, Alena Gros¹

¹VHIO Vall D'Hebron Institute of Oncology, Barcelona, Spain,²National Cancer Institute (NCI), Bethesda, WA,³IDIBELL-Institut Catala d’Oncologia, Barcelona, Spain,⁴The Francis Crick Institute, London, United Kingdom,⁵Early Cancer Institute, University of Cambridge, Cambridge, United Kingdom

摘要 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. Genmab B.V.; GSK; Glycotope Gmbh; Incyte Biosciences; Incyte Corporation; ICO; Kura Oncology Inc.; Lilly; S.A; Loxo Oncology Inc.; Macrogenics Inc.; Menarini Ricerche Spa; Merck; Sharp & Dohme S.A. Other, Personal fees. 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.

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