T-cell surface glycoprotein CD8 and tumor-associated antigen (CD8 x TAA) (CD8 x TAA)

The target CD8 on T cells and an undisclosed tumor-associated antigen refers to a bispecific therapeutic strategy designed to bridge cytotoxic T cells directly to tumor cells. CD8 is a cell surface glycoprotein found predominantly on cytotoxic T lymphocytes that acts as a co-receptor for the T-cell receptor by binding to MHC class I molecules (UniProt: P01732). In this bispecific configuration, one arm of the antibody or protein scaffold binds to CD8, while the other arm binds to a tumor-associated antigen (TAA) expressed on the surface of cancer cells. This dual engagement bypasses the traditional MHC-restricted TCR recognition, creating an artificial immunological synapse that triggers the release of cytotoxic granules, such as perforin and granzymes, leading to the destruction of the target tumor cell (PubMed: 33033171). Unlike traditional CD3-based T-cell engagers, CD8-selective agents specifically recruit the cytotoxic T-cell subset, potentially avoiding the activation of regulatory T cells and reducing the risk of systemic cytokine storms (PubMed: 30635554). This strategy is being explored in oncology to enhance the precision and safety of T-cell redirecting therapies. Clinical development of such agents often focuses on solid tumors where T-cell infiltration is a limiting factor for efficacy. Safety concerns associated with this class include cytokine release syndrome and potential off-target toxicity if the TAA is expressed on healthy tissues.

Other names

CD8-targeted bispecific T-cell engagerCD8-TCBCD8-redirecting bispecific antibodyCD8-selective T-cell engager

Simultaneous binding to the CD8 co-receptor on cytotoxic T cells and a tumor-associated antigen on malignant cells to induce T-cell mediated lysis.