Adoptive γδT-cell transfer alone or combined with chemotherapy for the treatment of advanced esophageal cancer

Abstract

Background aimsAfter therapy with platinum, 5-fluorouracil and taxane, no further recommended therapy is available for recurrent or metastatic esophageal cancer (r/mEC). Here the authors report two phase 1 trials of adoptive γδT-cell therapy, one for treatment-refractory r/mEC (γδT-monotherapy-P1, UMIN000001419) and the other for r/mEC with no prior systemic therapy (DCF-γδT-P1, UMIN000008097). MethodsFor γδT-monotherapy-P1, patients received four weekly and four biweekly injections of autologous γδT cells. For DCF-γδT-P1, patients received docetaxel, cisplatin and 5-fluorouracil (DCF) chemotherapy consisting of docetaxel (60 mg/m2) and cisplatin (60 mg/m2) on day 1 and continuous injection of 5-fluorouracil (600 mg/m2/day) on days 1–5 of each 28-day cycle; additionally, they received autologous γδT-cell injections on day 15 and day 22 of each cycle. ResultsTwenty-six patients were enrolled for γδT-monotherapy-P1. No severe adverse events were associated with γδT-cell therapy. Median overall survival was 5.7 months (95% confidence interval [CI], 4.3–10.0), and median progression-free survival was 2.4 months (95% CI, 1.7–2.8). Eighteen patients received DCF-γδT-P1. All treatment-related adverse events were associated with DCF chemotherapy, not γδT injection. Median overall survival was 13.4 months (95% CI, 6.7–not reached), and median progression-free survival was 4.0 months (95% CI, 2.5–5.7). The response rate and disease control rate were 39% and 78%, respectively. ConclusionsThe use of γδT-cell immunotherapy with or without chemotherapy was safe and feasible for r/mEC patients. Although the authors failed to demonstrate any clinical benefit of γδT-monotherapy-P1, survival benefits were observed in the DCF-γδT-P1 trial.