B- and T-lymphocyte attenuator (BTLA) (BTLA)

B- and T-lymphocyte attenuator (BTLA), also known as CD272, is an inhibitory receptor belonging to the immunoglobulin superfamily, structurally related to CTLA-4 and PD-1 (UniProt Q7Z6A9). It is expressed on the surface of T cells, B cells, and other immune cells, where it interacts with its ligand, Herpesvirus entry mediator (HVEM), to deliver a potent inhibitory signal that suppresses lymphocyte activation and proliferation (PubMed: 12796776). Unlike other checkpoint receptors that bind to B7 family members, BTLA is unique in its interaction with a TNF receptor superfamily member (HVEM). In the context of oncology, many tumors exploit the BTLA-HVEM pathway to evade immune surveillance, making BTLA a significant target for cancer immunotherapy (PubMed: 32814618). Tiflamimab (JS004) is a humanized monoclonal antibody designed to block BTLA, thereby restoring the immune system's ability to recognize and destroy malignant cells (ClinicalTrials.gov: NCT04137900). Clinical investigations are currently evaluating tiflamimab both as a monotherapy and in combination with PD-1 inhibitors for various solid tumors and lymphomas. Beyond cancer, BTLA's role in maintaining peripheral tolerance suggests potential applications in treating autoimmune and inflammatory disorders.

Other names

CD272B- and T-lymphocyte-associated proteinBTLA1

Tiflamimab is a humanized monoclonal antibody that acts as an antagonist by binding to BTLA and blocking its interaction with the ligand Herpesvirus entry mediator (HVEM), thereby preventing inhibitory signaling and enhancing T-cell mediated anti-tumor activity.