“…These T cells are genetically altered to express optimized TCRs that operate under restriction of the TCR-peptide-MHC complex, but offer the benefits of the full spectrum of activation signals that are exhibited by the wild-type receptor(4, 5), show more physiologically-relevant levels of affinity for their cognate antigen(6), and can also be directed against antigen-expressing stromal cells and intracellular TAAs(7). Antigens that have been targeted by TCR engineering, to date, have included relatively immunogenic antigens derived from spontaneously occurring tumor-specific T cells in patients, such as the melanocyte differentiation antigens MART-1(8), glycoprotein 100 (gp100)(9), the melanoma-associated antigen (MAGE)(10), and New York esophageal squamous cell carcinoma antigen (NYESO1)(11). Using these targets, anti-tumor responses have been reported in a subset of patients enrolled in early phase clinical trials of TCR-engineered T cells targeting melanoma(1, 9), colon cancer(12), and synovial cell sarcoma(13).…”