Manufacturing personalized CAR-T cells for cancer patients.
TCR = T cell receptor ACT = Adoptive Cell Transfer
"Developing a clinical-grade approach to efficiently isolate multiple TCRs that specifically recognize mutated peptides presented by any of a patient’s six human leukocyte antigen (HLA) class I alleles and subsequently engineer them back into autologous T cells for ACT therapy would open a new way to potentially treat refractory cancers. This goal has been limited by the large diversity of HLA class I alleles in the human population, with over 24,000 alleles currently recorded, and the polymorphic nature of the great majority of mutational antigenic determinants recognized by T cells. This is the reason why most current TCR-engineered T-cell therapies are limited to patients with HLA-A:02*01 haplotype." (A major limitation.)
"In the current study, we describe the development of a highly sensitive approach for efficient isolation of multiple TCRs specific for mutational neoantigens. This approach uses personalized libraries of hundreds of predicted neoantigen peptide sequences presented by the individual patient’s HLA class I alleles, and a targeted, non-viral gene editing approach to reconstitute the specificity of the isolated neoTCRs in a time-efficient process to generate clinical-grade neoTCR transgenic T cell preparations for ACT (Figure 1a)."