Definition

A preparation of autologous tumor infiltrating lymphocytes (TILs) genetically engineered to express a co-stimulatory antigen receptor (CoStAR) specific for folate receptor alpha (FolRa; FOLR1) and linked to the co-stimulatory domains CD28 and CD40, with potential immunomodulating and antineoplastic activities. Upon administration, the anti-FOLR1 CoStAR-expressing autologous TILs ITIL-306 specifically target, bind to and kill the FOLR1-expressing tumor cells. In addition, ITIL-306, by binding to FOLR1, is able to activate the TILs through the costimulatory signals. This increases T-cell proliferation and activation in the tumor microenvironment (TME), thereby enhancing the T-cell-mediated anti-tumor immune response against the FOLR1-expressing tumor cells. FOLR1 is a glycosylphosphatidylinositol linked cell-surface glycoprotein that is widely expressed in certain cancers while its expression is limited in normal tissues. CoStAR provides synthetic costimulation in the TME and increases T-cell proliferation and survival, and improves the effector function of T cells, which may boost the efficacy of TILs.