Cytotoxic T-lymphocyte-associated protein 4 and tumor-associated antigen (CTLA-4 x TAA)

Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and an unspecified tumor-associated antigen (TAA) represent a dual-target therapeutic strategy typically realized through bispecific antibodies. CTLA-4 is a potent inhibitory receptor expressed on T cells that maintains self-tolerance by outcompeting the costimulatory receptor CD28 for binding to B7 ligands (CD80/CD86) on antigen-presenting cells [1, 2]. While systemic CTLA-4 blockade has revolutionized oncology, its clinical utility is often hampered by significant immune-related adverse events (irAEs) resulting from non-specific T-cell activation [3]. By tethering a CTLA-4 antagonist to a TAA-binding domain, drug developers aim to localize the checkpoint inhibition to the tumor microenvironment, thereby increasing the local concentration of activated T cells while sparing peripheral tissues [4]. This approach is designed to improve the therapeutic index of CTLA-4-targeted therapies, potentially allowing for higher dosing and better efficacy in treating various solid tumors [5].

Other names

CTLA-4/TAA bispecificTumor-targeted CTLA-4 blockadeCTLA4-TAABispecific CTLA-4 target

Simultaneous binding to CTLA-4 on T-lymphocytes and a tumor-associated antigen on tumor cells to localize immune checkpoint blockade and enhance tumor-specific immune responses.