De Novo T-Cell Receptor (TCR) Discovery & Maturation
T cell receptor (TCR)-T cell therapy represents an alternative to CAR-T that offers several advantages. First, the repertoire of targetable antigens for TCR-T cell therapy is larger than for CAR-T cells. TCR-T cells can recognize epitopes derived from both membrane and intracellular proteins, including neoantigens harboring nonsynonymous SNPs that drive tumor development, while CAR-T cells are limited to targeting cell surface antigens. Second, the epitope density required to induce activation is lower for TCR-T cells than for classical CAR-T cells. Last, the high avidity of TCR-T cells may improve their efficacy, and the lower affinity of TCR to their target compared to CAR may allow each TCR-T cell to bind to several antigen-presenting tumor cells. An approach to unbiasedly discover and mature neoantigen-specific T cell receptor (TCR) is the use of a synthetic TCR variable domain library. BiCell Scientific’s synthetic TCR library is constructed from a consensus framework derived from > 10,000 unique TCRα and TCRβ chain sequences in the IMGT database. The constant framework is combined with designed variations in the CDR3 of both TCR alpha and beta chain that comprise the highly variable antigen-binding interface. Randomization of residue composition in the CDR3 is achieved by using a mixed pool of timer phosphoramidites to match target codon frequency. The resulting synthetic TCR library contains >1 × 108 unique single-chain TCR clones that are able to be expressed and displayed on the yeast cell surface. Customers select antigen epitope and MHC-I/II Tetramer from NIH Tetramer Core Facility. By differential sorting against MHC-I/II +/– epitope, BiCell Scientific’s de novo TCR discovery & maturation service can guarantee the selection of T-cell receptor sequences with selective binding to a custom antigen payload. BiCell Scientific’s TCR-T transfection virus is offered as MSCV-retrovirus or HIV-lentivirus. MSCV (Murine Stem Cell Virus) transduces T cells better than MoMuLV (Moloney Murine Leukemia Virus). The TCR-T transfection virus also expresses the GFP marker protein to facilitate FACS sorting applications.