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

J Nakajima, T Murakawa, T Fukami… - European Journal of …, 2010 - academic.oup.com
J Nakajima, T Murakawa, T Fukami, S Goto, T Kaneko, Y Yoshida, S Takamoto, K Kakimi
European Journal of Cardio-Thoracic Surgery, 2010academic.oup.com
Objectives: Human γδ T lymphocytes can recognise and kill non-small-cell lung cancer cells
by Vγ9Vδ2 T-cell receptor and/or NKG2D. We have established large-scale ex vivo
expansion of γδ T cells by zoledronate and interleukin-2. This pilot feasibility study evaluates
the safety and potential anti-tumour effects of activated autologous γδ T cells administered
intravenously to patients. Methods: Patients who had measurable foci of recurrent non-small-
cell lung cancer were registered to undergo γδ T-cell immunotherapy, designed as a one …
Abstract
Objectives: Human γδ T lymphocytes can recognise and kill non-small-cell lung cancer cells by Vγ9Vδ2 T-cell receptor and/or NKG2D. We have established large-scale ex vivo expansion of γδ T cells by zoledronate and interleukin-2. This pilot feasibility study evaluates the safety and potential anti-tumour effects of activated autologous γδ T cells administered intravenously to patients. Methods: Patients who had measurable foci of recurrent non-small-cell lung cancer were registered to undergo γδ 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 γδ T-cell fraction was proliferated and it was intravenously reinfused to the patient. Results: Ten patients had undergone the γδ T-cell immunotherapy. They were administered autologous γδ 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 γδ T-cell immunotherapy might be safe and feasible for patients with recurrent non-small-cell lung cancer.
Oxford University Press