A phase I study of adoptive immunotherapy for recurrent non-small-cell lung cancer patients with autologous Î3Î ́ T cells

Objectives: Human gd T lymphocytes can recognise and kill non-small-cell lung cancer cells by Vg9Vd2 T-cell receptor and/or NKG2D. We have established large-scale ex vivo expansion of gd T cells by zoledronate and interleukin-2. This pilot feasibility study evaluates the safety and potential anti-tumour effects of activated autologous gd Tcells administered intravenously to patients. Methods: Patients who had measurable foci of recurrent non-small-cell lung cancer were registered to undergo gd T-cell immunotherapy, designed as a one-way, open, clinical research, after their informed consent. Mononuclear cells collected from peripheral blood of the patient were cultured with zoledronic acid and interleukin-2. After 2-week incubation, the gd T-cell fraction was proliferated and it was intravenously reinfused to the patient. Results: Ten patients had undergone the gd T-cell immunotherapy. They were administered autologous gd T cells 3—12 times (mean = 6) every 2 weeks. No patient died during the study period. Adverse events, not directly related to the immunotherapy, were observed five times in four patients (grade 3 pneumonia in two and grade 1 coldness in three). According to the Response Evaluation Criteria in Solid Tumours, neither complete nor partial response was achieved in any patient; stable disease was observed in three; and progressive disease in five at 4 weeks after six consecutive injections of during immunotherapy. The Functional Assessment of Cancer Therapy-Biologic Response Modifier scores of the patients during immunotherapy were stable or improved, except for one patient who had suffered from pneumonia. The patients were followed up after immunotherapy for 240—850 days (median = 401 days). At the end of the observation, six patients were alive. Conclusions:We suggest that gd Tcell immunotherapy might be safe and feasible for patients with recurrent non-small-cell lung cancer. # 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.