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

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).

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.

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.

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.

Cytotherapy. 2017 Feb 07 [Epub]

Taku Aoki, Hirokazu Matsushita, Mayumi Hoshikawa, Kiyoshi Hasegawa, Norihiro Kokudo, Kazuhiro Kakimi

Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, The University of Tokyo, Tokyo, Japan; Second Department of Surgery, Dokkyo Medical University, Mibu, Tochigi, Japan., Department of Immunotherapeutics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan., Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, The University of Tokyo, Tokyo, Japan., Department of Immunotherapeutics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: This email address is being protected from spambots. You need JavaScript enabled to view it..