T cell receptor recognizing RCC-26-derived peptide–MHC complexes (TCR53)

The T cell receptor recognizing RCC-26-derived peptide–MHC complexes, specifically known as TCR53, is a high-avidity αβ T cell receptor originally isolated from tumor-infiltrating lymphocytes of a patient with renal cell carcinoma (RCC). It specifically recognizes a shared tumor-associated antigen presented by the HLA-A*02:01 major histocompatibility complex, which is naturally expressed on the RCC-26 cell line. This antigen is found in over 60% of RCC cases and approximately 25% of other malignancies, while remaining absent in normal tissues, making it a promising target for immunotherapy. TCR53 has been genetically modified through codon optimization and murinization to enhance its expression and functional avidity in engineered T cells. These modified T cells are used in adoptive T-cell therapy (TCR-T) to target and eliminate cancer cells expressing the cognate peptide-MHC complex. Research indicates that the recognized epitope may be derived from human endogenous retrovirus (HERV) sequences, such as HERV-E, which are selectively reactivated in certain tumors. Therapeutic strategies also explore combining TCR53 with chimeric costimulatory receptors, such as PD-1:28, to overcome immunosuppression in the tumor microenvironment.

Other names

TCR-53TCR53mcRCC-26-specific T cell receptorHLA-A2-restricted RCC-specific TCR

Adoptive T-cell therapy