Abstract 4071: Identification of myeloma-specific T cell receptors by functional single cell interaction analyses

• Published in: Cancer research (Chicago, Ill.) Vol. 83; no. 7_Supplement; p. 4071
• Main Authors: Wagner, Tim R., Boğa, Eren, Schmidt, Patrick, Osen, Wolfram, Platten, Michael, Goldschmidt, Hartmut, Raab, Marc S., Friedrich, Mirco J., Eichmüller, Stefan B.
• Format: Journal Article
• Language: English
• Published: 04.04.2023
• ISSN: 1538-7445; 1538-7445
• DOI: 10.1158/1538-7445.AM2023-4071

Abstract Innovative immunotherapy approaches such as adoptive transfer of chimeric antigen receptor (CAR) T cells or tumor infiltrating lymphocytes (TILs) have shown great success in the treatment of solid tumors and hematological malignancies. Although treatment of multiple myeloma with CAR T cells can induce deep responses, relapses frequently occur due to antigen escape and limited CAR T cell persistence. TCR-engineered T cells may mediate sustained antitumor effects upon recognition of intracellular targets, thereby significantly increasing the range of relevant target antigens. In our project, we propose to identify T cell receptors (TCRs) specifically targeting autologous myeloma cells. Tumor-reactive T cells were identified using the Berkeley Lights Lightning platform, allowing simultaneous functional analysis of up to 1500 individual T cell/target cell interactions per run. Reactive T cells have been identified upon detection of secreted chemokines (IFNγ, TNFα, IL-2) and by measurement of CD137 surface expression. Tumor-reactive T cells showing various cytokine secretion patterns and CD137 expression profiles could be detected in each myeloma patient (7 to 26 of approx.1200 cells tested per patient). Individual tumor reactive T cells have been isolated for TCR sequencing. Recovered TCR genes will be cloned and overexpressed in autologous T cells for functional validation and analysis of tumor derived neoepitope specificity. In summary, we present a pipeline allowing identification of myeloma-recognizing T cells and recovery of bona fide tumor-reactive TCRs eligible for patient-individualized T cell therapy. Citation Format: Tim R. Wagner, Eren Boğa, Patrick Schmidt, Wolfram Osen, Michael Platten, Hartmut Goldschmidt, Marc S. Raab, Mirco J. Friedrich, Stefan B. Eichmüller. Identification of myeloma-specific T cell receptors by functional single cell interaction analyses. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4071.