T-cell triggering thresholds can be edited by engineered TCR with enhanced affinity. TAEST (TCR affinity enhanced specific T-cells) for NY-ESO-1 was generated, and the TCR had 29 X higher affinity to its antigen vs wild type T-cells and with good (80-90%+) expression. There was good in vitro (CTL/ELISPOT) and in vivo efficacy with strong evidence of tumor specific TAEST infiltration. TAEST, with its enhanced TCR affinity, is safe and showed encouraging efficacy (4/7 showed response and 3/7 SD) and safety profile in a Phase I study. Lymphodepletion pretreatment appeared to be critical for efficacy/cytokine response/persistence of TAEST cells.