T-cell receptor recognizing Cell division cycle-associated protein 1-derived peptide–MHC complexes (TCR-CDCA1-pMHC)

The T-cell receptor (TCR) recognizing CDCA1-derived peptide–MHC complexes is a specialized immune receptor designed to target cancer cells overexpressing Cell division cycle-associated protein 1 (CDCA1), also known as NUF2. CDCA1 is a component of the NDC80 kinetochore complex, which is essential for proper chromosome segregation during mitosis (PMID: 12393510). While CDCA1 is highly expressed in various malignancies—including lung, esophageal, and head and neck cancers—its expression in normal adult tissues is largely restricted to the testis, classifying it as a cancer-testis antigen (PMID: 16618915). TCRs specific for CDCA1 peptides, such as those restricted by HLA-A*24:02, are utilized in adoptive cell therapies where patients' T cells are engineered to express these receptors (PMID: 30104315). Upon binding to the peptide-MHC complex on the tumor surface, the TCR initiates a signaling cascade that leads to the directed lysis of the malignant cell. This target represents a precision immunotherapy approach aimed at leveraging the high tumor-specificity of CDCA1 to minimize systemic side effects. Clinical development has focused on TCR-engineered T-cell (TCR-T) products like TBI-1501 for solid tumors (NCT03578406). The efficacy of this target depends on both the presence of the specific HLA allele and the expression level of the CDCA1 protein within the tumor microenvironment.

Other names

CDCA1-specific T-cell receptorNUF2-specific T-cell receptorT-cell receptor recognizing NUF2-derived peptide-MHCTCR recognizing CDCA1-derived peptide-HLA complexes

The TCR-engineered T cells express a receptor that specifically binds to the CDCA1 peptide-HLA complex (e.g., CDCA1-63 peptide on HLA-A*24:02) on tumor cells, leading to T-cell activation, secretion of inflammatory cytokines such as IFN-gamma, and direct cytotoxic killing of the cancer cells via the perforin/granzyme pathway (PMID: 24333715).