Adjuvant combination therapy with gemcitabine and autologous γδ T-cell transfer in patients with curatively resected pancreatic cancer.

BACKGROUND AIMS: The outcome for pancreatic cancer after surgery remains highly unsatisfactory, and development of more effective therapies is urgently needed. Therefore, we conducted a phase I clinical study of a novel combination of gemcitabine (GEM) and autologous γδ T-cell therapy for patients with curatively resected pancreatic cancer (University Hospital Medical Information Clinical Trials Registry identifier 000000931).

METHODS: From July 2008 to December 2012, 56 consenting patients were recruited. After preliminary testing of γδ T-cell proliferative capacity, 28 patients were eligible to receive combined GEM plus γδ T-cell therapy.

RESULTS: During treatment, most of the adverse events observed were due to GEM, including myelosuppression and gastrointestinal disorders. No severe adverse events were obviously related to the γδ T-cell therapy. To evaluate clinical efficacy, patients receiving combined therapy (Group A, n = 28) were compared with those receiving GEM alone (Group B, n = 20). No significant differences were observed between the two groups in recurrence-free survival or overall survival. However, we found that, relative to progressing patients, more γδ T-cells were detectable in the blood of recurrence-free patients after only two injections (P < .0388) and more so five injections (P < .0175). Patients with >15% peripheral γδ T-cells after two injections and >20% after five injections had a chance of a more favorable clinical outcome. Accumulation of γδ T cells was positively related to the quality of the infused products, with those having >80% γδ T cells being optimal.

DISCUSSION: High quality of the γδ T-cell product is crucial to achieve a high percentage of γδ T cells in the blood and to achieve better clinical outcome.