Experimental study on the treatment of intracerebral glioma xenograft with human cytokine-induced killer cells.
Objective. To investigate the phenotype changes and proliferation activities of cytokine-induced killer cells (CIKs) and lymphokine-activated killer cells (LAKs) from healthy donor, and the cytotoxicities of CIKs and LAKs to human in vitro glioma cell lines U251 and U87. Therapy of CIK intratumoral injection was evaluated in nude mouse models. Methods. CIK cells were induced from peripheral blood mononuclear cells (PBMC) of healthy donors with multiple cytokines. Phenotype analysis of CIKs and LAKs was performed with flow cytometer (FCM). The specific cytotoxicities of CIKs and LAKs against cell line U251 and U87 were determined by LDH method. After intracerebral injection of CIKs, the distribution of CIKs and the inflammatory reaction of their surrounding brain tissue were observed through continuous pathological sections. In vivo anti-tumor activity of CIKs was evaluated in athymic nude mice with intracerebral xenotransplanted U251 glioma by MRI. Results. Amount of CIKs was increased (49.83+/-2.04) times and double positive cells, CD3(+)/CD56(+) cells, were increased from (3.36+/-1.85%) to (44.07+/-14.14%) with elevated absolute amount over 1000 times after 2 week culture. In vitro experiments demonstrated that compared with LAK, CIKs possessed more obvious cytotoxic activity to U251 and U87. In vivo experiments showed that there was no severe inflammatory reaction in brain tissue. CIKs can markedly inhibit intracranial xenotransplanted glioma growth by intracranial injection (P<0.01). Conclusion. CIKs are a kind of highly effective immune cells which have a strong suppressive effect on growth for in vitro and in vivo glioma. Local injection of CIKs does not produce severe damage to normal brain tissue and is likely to be used in clinical adoptive immunotherapy of intracerebral glioma.
Department of Neurosurgery and Neuro-oncology, Key Laboratory of Cancer Prevention and Therapy, Cancer Institute and Hospital of Tianjin Medical University, Tianjin 300060, China.
Peng
P
Wang
Jin-Pu
JP
Yu
Song-Yuan
SY
Gao
Xiu-Mei
XM
An
Xiu-Bao
XB
Ren
Xiao-Guang
XG
Wang
Wen-Liang
WL
Li
D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology*; D005910:Glioma / Q000276:immunology / Q000473:pathology / Q000628:therapy; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000637:transplantation*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation / Q000276:immunology*; D010641:Phenotype; D014183:Transplantation, Heterologous / Q000276:immunology*; D014407:Tumor Cells, Cultured
D016207:Cytokines