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cancer, cancer cellsIn the current study
CANCER, POINT MUTATIONS
The ultimate goal of any cancer therapy is to target and kill cancer cells while sparing normal cells. The human immune system is suited to achieve this goal owing to the specificity of TCRs. These receptors can distinguish single point mutations in the cancer genome that change the amino acid sequences of peptides presented by the major histocompatibility complex (MHC) on the cell surface of cancer cellsIn the current study, we describe an approach that enables efficient isolation of multiple TCRs specific for mutational neoantigens. This strategy uses personalized libraries of hundreds of predicted neoantigen peptide sequences presented by HLA class I alleles of an individual patient and a targeted, non-viral gene-editing method to reconstitute the specificity of the isolated neoTCRs. Overall, this time-efficient process is able to generate clinical-grade neoTCR transgenic T cell preparations for ACT (Fig. 