过继性细胞移植
医学
免疫疗法
细胞毒性T细胞
癌症
T细胞
颗粒酶B
免疫学
癌症研究
离体
癌症免疫疗法
CD8型
颗粒酶
抗原
免疫系统
穿孔素
生物
体内
内科学
体外
生物技术
生物化学
作者
Makoto Kondo,Kazuko Sakuta,Atsutaka Noguchi,Naoko Ariyoshi,Keisuke Sato,Soichiro Sato,Akihiro Hosoi,Jun Nakajima,Yukihiro Yoshida,Kenshiro Shiraishi,Kiyoharu Nakagawa,Kazuhiro Kakimi
出处
期刊:Cytotherapy
[Elsevier]
日期:2008-01-01
卷期号:10 (8): 842-856
被引量:133
标识
DOI:10.1080/14653240802419328
摘要
Human gammadelta T cells can be activated by phospho-antigens and aminobisphosphonates such as zoledronate. Because they can kill tumor cells in a major histocompatibility complex (MHC)-unrestricted manner, adoptive transfer of activated gammadelta T cells may represent a novel cancer immunotherapy. We tested whether gammadelta T cells from advanced cancer patients can be expanded by zoledronate.Peripheral blood mononuclear cells from healthy donors and patients with advanced non-small cell lung cancer, bone metastatic breast or prostate cancer, or lung metastatic colorectal cancer, were stimulated with zoledronate (5 microM) and interleukin (IL)-2 (1000 IU/mL) for 14 days. The phenotype and function of the expanded gammadelta T-cell populations from healthy donors and cancer patients were compared.Gammadelta T cells from cancer patients and healthy donors responded to zoledronate equally well in terms of both phenotype and function. gammadelta T cells grew rapidly in vitro and expression of effector molecules, such as interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, perforin, granzyme B, FasL and TRAIL, increased over time. Cytotoxicity peaked on days 12-14, and proliferation continued up to 14 days, during which time>1x10(9) gammadelta T cells could be obtained from a starting sample of 45-70 mL peripheral blood.Using the agent zoledronate, already widely used in the clinic, we have established that efficient large-scale ex vivo expansion of gammadelta T cells from cancer patients is possible. These cells exert potent cytotoxicity and may be used for autologous cellular immunotherapy of cancer.
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