A phase I study of adoptive immunotherapy for recurrent non-small-cell lung cancer patients with autologous gammadelta T cells.
OBJECTIVE
Human gammadelta T lymphocytes can recognise and kill non-small-cell lung cancer cells by Vgamma9Vdelta2 T-cell receptor and/or NKG2D. We have established large-scale ex vivo expansion of gammadelta T cells by zoledronate and interleukin-2. This pilot feasibility study evaluates the safety and potential anti-tumour effects of activated autologous gammadelta T cells administered intravenously to patients.


METHODS
Patients who had measurable foci of recurrent non-small-cell lung cancer were registered to undergo gammadelta 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 gammadelta T-cell fraction was proliferated and it was intravenously reinfused to the patient.


RESULTS
Ten patients had undergone the gammadelta T-cell immunotherapy. They were administered autologous gammadelta 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 gammadelta T-cell immunotherapy might be safe and feasible for patients with recurrent non-small-cell lung cancer.
Department of Cardiothoracic Surgery, The University of Tokyo Graduate School of Medicine, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. nakajima-tho@h.u-tokyo.ac.jp
Jun
J
Nakajima
Tomohiro
T
Murakawa
Takeshi
T
Fukami
Shigenori
S
Goto
Toru
T
Kaneko
Yukihiro
Y
Yoshida
Shinichi
S
Takamoto
Kazuhiro
K
Kakimi
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000556:secondary / Q000628:therapy*; D002478:Cells, Cultured; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000097:blood; D008175:Lung Neoplasms / Q000628:therapy*; D008207:Lymphatic Metastasis; D008213:Lymphocyte Activation; D017710:Lymphocyte Transfusion / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000628:therapy; D011788:Quality of Life; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000637:transplantation; D016896:Treatment Outcome
D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma