Tu203 - Circulating Tumor DNA and T Cells Expressing PD-1 and CD39 Enable Neoantigen-targeted T-cell Therapies from Liquid Biopsies

Imma Creus; Ana Belen Moreno; Carlos Alberto Fajardo; maria Lozano-Rabella; Ricardo Pujol; Anna Yuste-Estevanez; Albert Marin; Jared Gartner; Jonatan Gonzalez; Elena Elez; Irene Braña; Vladimir Galvao; Rebeca Sanz; Cristina Saura; Eva Muñoz; Ramon Alemany; Josep Tabernero; Rodrigo Toledo; Elena Garralda; Alena Gros

Abstract Text: Lymphocytes targeting neoantigens play an important role in the antitumor efficacy of cancer immunotherapies. However, the strict need of a tumor biopsy both to identify candidate neoantigens and reactive T cells or TCRs can underestimate tumor heterogeneity in the advanced metastatic setting and limits the broad applicability of personalized T-cell therapies. Here, we explored the concomitant detection of non-synonymous mutations via WES and isolation of neoantigen-specific T cells and TCRs using liquid biopsies from patients with metastatic breast, gynecological, colorectal or head and neck cancers of epithelial origin and compared to those detected in the tumor. Biomarker-based isolation of circulating CD8+ and CD4+ T cells allowed the identification of neoantigen-specific T cells in five of six patients, being PD-1hiCD39+ the combination that most consistently captured CD8+ and CD4+ neoantigen reactivities. WES of cfDNA from six patients preferentially identified clonal somatic mutations from tumor biopsies and enabled the detection of seven of 13 neoantigen-specific T-cell responses in four of five patients harboring neoantigen reactivities. Our results underscore peripheral blood as an alternative source to identify cancer-specific neoantigens and CD8+ and CD4+ neoantigen-specific T lymphocytes and TCR from patients with epithelial cancers, bearing important implications for monitoring and exploiting personalized T-cell responses in cancer patients.