Discovering tumor-reactive T-cell receptors through single-cell sequencing of tumor-infiltrating lymphocytes

Autor: Cynthia Timmers, Bulent Arman Aksoy, Aubrey S. Smith, Elinor Gottschalk, Pinar Aksoy, Chrystal M. Paulos, Hannah M. Knochelmann, Jeff Hammerbacher, Martin J. Romeo, Linda Macpherson, Caroline Mart, Mark P. Rubinstein, Marzena Swiderska-Syn, John Wrangle
Rok vydání: 2021
Předmět:
Popis: We evaluated the utility of single-cell sequencing of tumor-infiltrating lymphocytes (TIL) for tumor-reactive T-cell receptor (TCR) discovery. Using the MC38 cell line as our tumor model in mice, we show that expression of exogenous TCRs via mRNA electroporation in human T cells provides an easy and quick path to validating tumor-specific candidate TCRs. We detail the identification and validation of four novel MC38-reactive mouse TCRs with varying levels of reactivity to the target cells. Validating our process, one of the MC38 TCRs is specific against a previously reported neoantigen (ASMTNMELM in the Adpgk gene). Consideration of these methodologies may aid in the development of rapid TCR-based therapies for the treatment of cancer and human disease.Abstract Figure
Databáze: OpenAIRE