NY-ESO-1-specific CD4+ T cell receptor (NY-ESO-1 CD4+ TCR) (NY-ESO-1 CD4+ TCR)

NY-ESO-1-specific CD4+ T cell receptors are engineered or naturally occurring receptors that recognize the cancer-testis antigen NY-ESO-1 (encoded by CTAG1B) when presented by HLA class II molecules, most notably HLA-DPB1*04:01 (Zhao et al., 2007, PubMed: 17172428). NY-ESO-1 is highly expressed in various malignancies, including synovial sarcoma, melanoma, and ovarian cancer, while its expression in normal tissues is restricted to the testes and placenta, making it an ideal target for immunotherapy (Gnjatic et al., 2006, PubMed: 16461460). CD4+ T cells expressing these TCRs play a multifaceted role in the anti-tumor response, including the secretion of pro-inflammatory cytokines like IFN-gamma and TNF-alpha, providing essential help to CD8+ cytotoxic T cells, and in some cases, exerting direct cytotoxic effects on MHC class II-positive tumor cells (Hunder et al., 2008, PubMed: 18565860). In the context of adoptive cell therapy, patient T cells are transduced with genes encoding these specific TCR alpha and beta chains to create TCR-T cell products. These therapies aim to overcome the immunosuppressive tumor microenvironment and achieve durable clinical responses. Clinical development focuses on patient populations that are both NY-ESO-1 positive and possess the appropriate HLA restriction element, such as HLA-DP4 (Pollack et al., 2020, PubMed: 32015118). Safety monitoring for these therapies includes assessing for cytokine release syndrome and potential off-target effects, although the restricted expression of NY-ESO-1 minimizes the risk of healthy tissue damage.

Other names

NY-ESO-1-specific T-cell receptorCD4+ T-cell receptor recognizing NY-ESO-1/HLA-DPB1*04CTAG1B-specific CD4+ TCRNY-ESO-1/HLA-DP4-specific TCRCancer/testis antigen 1B-specific CD4+ TCR

Adoptive T-cell therapy where T cells are engineered to express a TCR that recognizes NY-ESO-1 peptides presented by HLA class II molecules, facilitating targeted destruction of tumor cells and enhancement of the broader immune response through cytokine secretion and CD8+ T cell support.