T-cell receptor (TCR) recognizing NA17-A, MART-1, gp100, and tyrosinase peptides presented by HLA-A2 (TCR)

The T-cell receptor (TCR) recognizing NA17-A, MART-1, gp100, and tyrosinase peptides presented by HLA-A2 is a specialized immune receptor utilized in adoptive T-cell therapies for metastatic melanoma. These TCRs are designed to recognize melanoma-associated differentiation antigens (MAAs) such as MART-1 (Melan-A), gp100, and tyrosinase, as well as the tumor-specific antigen NA17-A, all of which are presented by the HLA-A*02:01 MHC molecule (Morgan et al., 2006; Shichijo et al., 1998). By engineering a patient's T cells to express these specific TCRs, the immune system is redirected to identify and eliminate cancer cells that express these intracellular markers (Rosenberg et al., 2008). This strategy is particularly effective because it targets proteins that are highly prevalent in melanoma but absent in most normal tissues, with the notable exception of healthy melanocytes. Consequently, while these therapies can induce significant tumor regression, they are often associated with on-target, off-tumor toxicities in the skin, eyes, and ears, where normal melanocytes reside (Johnson et al., 2009). Clinical success depends on the precise matching of the TCR specificity to the patient's HLA type and the antigen profile of the tumor.

Other names

Melanoma-associated antigen-specific T-cell receptorHLA-A*02:01-restricted T-cell receptorMART-1-specific TCRgp100-specific TCRTyrosinase-specific TCRNA17-A-specific TCRMelanoma differentiation antigen-specific TCR

Engineered or endogenous T-cell receptors bind to specific peptide-MHC complexes (HLA-A*02:01 presenting melanoma-associated antigens) on the surface of tumor cells, triggering T-cell activation, cytokine release, and direct lysis of the cancer cell.