Background: The immunogenic cancer testis antigen NY-ESO-1 is expressed in several cancers. While NY-ESO-1 is not expressed in vital tissues, it is expressed in approximately 60% in advance myeloma (MM), 15% of ovarian (OC), 32% of advanced melanoma (Mel), 32 % in NSCLC, and 70% of synovial sarcoma (SS) tumors (based on TCGA). Expression is correlated with tumor proliferation and high risk features. An autologous T cell product bearing human-derived affinity-optimized T cell receptor (TCR) which recognizes the SLLMWITQC-HLA-A*A2 peptide complex (NY-ESO-1^c259-T) is investigated in several clinical trials Methods: Six clinical studies across 5 tumor types were initiated in HLA-A*02:01 positive patients (pts) with NY-ESO-1 expressing tumors. Fifty three pts have been treated with NY-ESO-1c259-T as of Jan 2016; 27 in MM and 26 in solid tumors. NCT01352286: phase I/II study in post-ASCT setting in pts with relapsed or refractory MM: 25 pts enrolled. NCT01892293: phase I/IIa non-transplant study in pts with relapsed or progressive MM: 2 pts enrolled. NCT01343043: pilot study in unresectable, metastatic, or recurrent SS: 16 pts enrolled: cohort 1 completed (n = 12); 2 additional cohorts have been added to evaluate conditioning and antigen level (4 pts treated across these cohorts to date). NCT01567891: phase I study in pts with refractory or platinum resistant OC and/or have received more than 2 lines of prior chemotherapy: 6 patients enrolled. NCT01350401: phase I study in pts with metastatic melanoma: 4 pts enrolled. NCT02588612: phase I/II study in pts with relapsed metastatic NSCLC: no pts enrolled. The main objectives are safety, tolerability, and efficacy. Biomarker objectives include persistence in peripheral of NY-ESO-1c259-T in blood, T-cell lineage and functionality of these cells over time; characterization of cytokine profiles, as well as NY-ESO-1 antigen levels post infusion. Clinical trial information: NCT01352286, NCT01892293, NCT01343043, NCT01567891, NCT01350401, NCT02588612