Safety profile and anti-tumor effects of adoptive immunotherapy using gamma-delta T cells against advanced renal cell carcinoma: a pilot study.
OBJECTIVE
Although various types of immunotherapy have been used to improve the prognosis of patients with advanced renal cell carcinoma (RCC), adoptive immunotherapy using gamma-delta (gammadelta) T cells has not yet been tried. In this study, we designed a pilot study of adoptive immunotherapy using in vitro activated gammadelta T cells against advanced RCC to evaluate the safety profile and possible anti-tumor effects of this study.


METHODS
Patients with advanced RCC after radical nephrectomy were administered via intravenous infusion in vitro-activated autologous gammadelta T cells every week or every 2 weeks, 6-12 times, with 70 JRU of teceleukin. Adverse events, anti-tumor effects and immunomonitoring were assessed. The anti-tumor effects were evaluated according to tumor doubling time (DT) by computed tomography (CT) and immunomonitoring was performed by flow cytometric analysis.


RESULTS
Seven advanced RCC patients were entered in this study. The most common adverse events were fever, general fatigue and elevation of hepatobiliary enzymes, but no severe adverse events were seen. Prolongation of tumor DT was seen in three out of five patients; these three patients showed an increase in the number of gammadelta T cells in peripheral blood and also a high response to the antigen in vitro.


CONCLUSIONS
The results indicated that adoptive immunotherapy using in vitro-activated autologous gammadelta T cells was well tolerated and induced anti-tumor effects.
Kobayashi
Hirohito
H
Department of Urology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. hirohitokobayashi-jua@umin.ac.jp
Tanaka
Yoshimasa
Y
Yagi
Junji
J
Osaka
Yukinari
Y
Nakazawa
Hayakazu
H
Uchiyama
Takehiko
T
Minato
Nagahiro
N
Toma
Hiroshi
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects*; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000628:therapy; D009392:Nephrectomy; D010865:Pilot Projects; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D014182:Transplantation, Autologous
D016692:Receptors, Antigen, T-Cell, gamma-delta