Abstract 901: Monitoring of Neoantigens and Adoptively Transferred Personalized NeoTCR T Cell Populations in the Tumor and PBMCs of Patients with Solid Tumors

Document Type

Abstract

Publication Date

4-4-2023

Publication Title

Cancer Research

Keywords

washington; isb

Abstract

Results: Patient 0503, a patient with MSS colorectal cancer, was treated with 3 unique neoTCRs (1.3x109 neoTCR+ cells) which targeted 2 distinct neoantigens presented by HLA-B*39:01 or HLA-C*12:02. Analysis of longitudinal biopsies confirmed that targeted mutations were truncal, with both neoantigens present pre- and post-dosing. NeoTCR+ T cells were identified in the tumor by RNA seq and imaging, with neoTCR+ T cells also expressing Granzyme B. Furthermore, single cell RNA seq of neoTCR+ T cells from the pre-infusion product as compared neoTCR T cells isolated from the patients’ blood 2 months post-infusion demonstrated evidence of antigen engagement in 1 out of 3 neoTCR T cell products, with a shift from a predominantly Tcm/Tem-like phenotype pre-infusion to a Teff-like state post-infusion. This neoTCR T cell product also increased slightly in the blood from 1.1 to 3.4% between month 1 and 2, while the other 2 T cell products remained predominantly in the Tcm-like phenotype and remained stable in the blood between month 1 and 2. Patient 0612, a patient with melanoma, was treated with 3 unique neoTCRs (4.0x109 neoTCR+ cells) which targeted 3 distinct neoantigens presented by HLA-B*08:01 or HLA-C*07:02. Longitudinal biopsies support the assessment that 2/3 mutations were truncal and 1 targeted mutation was sub-clonal based on their presence in each biopsy. Retrospective analysis showed HLA loss of heterozygosity at HLA-C07:02 in all 3 biopsies, affecting 2/3 infused TCR products. The remaining TCR showed evidence of a shift from a predominantly Tcm-like phenotype pre-infusion to more differentiated Teff/Tcm-em phenotypes post-infusion compared to the 2 TCRs targeting mutations expressed by the lost HLA allele.

Conclusion: These case studies illustrate for the first time tracking of 3 unique personalized T cell products within a single patient. Shifts in the T cell phenotype of the neoTCR T cell products post-infusion for some, but not all, of the products suggest early signs of T cell engagement with the target.

Clinical Institute

Cancer

Department

Institute for Systems Biology

Department

Oncology

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