Mutant RAS-specific T cell receptor (mutRAS TCR)

The T cell receptor (TCR) recognizing TG02 peptide–MHC complexes is a specialized immune receptor that specifically identifies neoantigens derived from oncogenic RAS mutations. TG02 is a peptide-based cancer vaccine developed by Targovax (now Circio) that consists of eight synthetic 17-mer peptides representing the most common mutations in the KRAS, NRAS, and HRAS genes at codons 12 and 13, such as G12D, G12V, and G13D. These mutations are critical drivers in various solid tumors, including pancreatic, colorectal, and lung cancers, and are absent in normal tissues, making them ideal targets for immunotherapy. The TCRs specific for these mutant peptides can be naturally induced and expanded by the TG02 vaccine or isolated and engineered for use in adoptive cell therapies, such as TCR-T or TCR-NK cells. Upon recognition of the mutant peptide presented by Major Histocompatibility Complex (MHC) molecules, the TCR initiates a potent immune response characterized by T cell activation, proliferation, and the direct killing of tumor cells. Clinical strategies often combine the TG02 vaccine with immune checkpoint inhibitors like pembrolizumab to overcome tumor-mediated immunosuppression and enhance the anti-tumor efficacy of the RAS-specific T cells.

Other names

RAS-specific T cell receptorTG02-induced T cell receptorNeoantigen-specific T cell receptorMutant RAS TCRT cell receptor recognizing TG02 peptide–MHC complexes

The T cell receptor (TCR) recognizes specific mutant RAS peptides presented by MHC molecules on the surface of tumor cells, triggering T cell activation, cytokine release (e.g., IFN-gamma), and granzyme/perforin-mediated lysis of the tumor cell.