T-cell receptor recognizing TCR gamma alternate reading frame protein (TARP)-derived peptide–MHC complexes (TARP-TCR)

The T-cell receptor (TCR) recognizing TARP-derived peptide–MHC complexes is a specialized immune receptor engineered for adoptive cell therapy against malignancies expressing the TCR Gamma Alternate Reading Frame Protein (TARP). TARP is a tumor-associated antigen that is highly expressed in over 95% of prostate cancers and approximately 50% of breast cancers, while its expression in normal tissues is largely restricted to the prostate (Wolfgang et al., 2000; Friedrich et al., 2010). The engineered TCR is designed to bind with high affinity to TARP-derived peptides, most commonly the TARP(4-13) epitope, presented by the HLA-A*02:01 major histocompatibility complex (Epel et al., 2008). This binding event triggers T-cell activation, proliferation, and the release of cytotoxic molecules such as granzymes and perforin, resulting in the targeted destruction of TARP-positive tumor cells (Maeda et al., 2004). Currently, this TCR is a key component in the development of TCR-T cell therapies aimed at treating metastatic castration-resistant prostate cancer and advanced breast cancer (NCI, 2023). Therapeutic challenges include managing on-target, off-tumor toxicity in the prostate and ensuring the persistence of engineered T-cells within the immunosuppressive tumor microenvironment.

Other names

TARP-specific T-cell receptorT-cell receptor recognizing TARP/HLA-A2TARP-directed T-cell receptorTARP-TCR-T

Engineered T-cells expressing the TARP-specific TCR recognize the TARP peptide (typically TARP 4-13) presented by HLA-A*02:01 on the surface of tumor cells, triggering T-cell activation, cytokine release, and targeted lysis of the cancer cells.