Definition

A preparation of T lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) specific for the human tumor-associated antigen (TAA) mesothelin (MSLN), and CD40 ligand (CD40L; CD154; TRAP; TNFSF5), with potential immunomodulating and antineoplastic activities. Upon administration, anti-MSLN CAR-CD40L-expressing T lymphocytes specifically target and kill MSLN-expressing tumor cells. Mesothelin, a cell surface glycoprotein involved in cell adhesion, is overexpressed in a variety of cancer cell types. CD40L binds to CD40 and activates CD40/CD40L-mediated signaling, which activates monocyte-derived dendritic cells (moDCs), increases the secretion of inflammatory cytokines and further stimulates cytotoxic T lymphocytes (CTLs). This enhances cytotoxicity and anti-tumor immune response.