[Establishment of a SCID mouse model for synergistic anti-tumor effect of human IL-12 and B7-1].
Human IL-12(hIL-12) has weak effect on mouse immunity cells, so the practical animal model is not available for the study of hIL-12 anti-tumor activity. In this work, the improved Winn assay was applied to evaluate the synergistic anti-tumor effects of hIL-12 and human costimulatory molecule B7-1(hB7-1) on human tumor in HuPBL-SCID mouse model. Three gene transferring solutions hIL-12, hB7-1 and their mixture(1:1) were prepared using the nonliposome transgene reagent and the expressing vectors, and hIL-12, hB7-1 or their mixture were transferred into tumor cell A375 respectively. Then A375 were co-injected into SCID mice with HuPBL, and rhIL-2 were injected i.p. as an anti-tumor agitator. On the other hand, LoVo and SPC tumor cells were also used to test the inhibitory effect of the mixture of hIL-12 and hB7-1. The anti-tumor effect of transferred genes was estimated by detecting tumor inhibition rate. Furthermore, the histochemical change of A375 implanting tumor tissue was also observed. Results showed that, to A375, the tumor inhibition rate of hIL-12, hB7-1, or their mixture were 74.06%, 66.98%, and 93.40%, respectively (P<0.01); and the mixture showed a good synergistic effect according to the Webb s fraction multiplication law. The tumor inhibition rate of the mixture in LoVo and SPC implanted mice were 98.37% and 97.39% respectively, also showing a good synergistic effect. Histochemical study in A375 implanted mice showed that in gene transfected mice, tumor cells were greatly inhibited and fully intruded by HuPBL cells; while in control group, tumor cells grew very well and HuPBL showed a conglomeration. At last, the human IgG and T cells in PBL of HuPBL-SCID mice were higher than non-HuPBL-SCID mice implanted A375; which showed that HuPBL-SCID mice could be applied for the evaluation of the anti-tumor effect of human IL-12 and B7-1. All data indicated that the combination of hIL-12 and hB7-1 gene might be a promising approach for in vivo cancer therapy.
Gao
Jun
J
Division of Epidemiology, Institute of Naval Medicine, Shanghai 200433, China. Gaojun111@yahoo.com.cn
Zhao
Ping
P
Chen
Xiou-Hua
XH
Li
Mao
M
Long
Jian-Qiou
JQ
Gu
Ai-Mei
AM
Wu
Xiao-Lan
XL
Cao
Guang-Wen
GW
Qi
Zhong-Tian
ZT
D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics*; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
D018122:B7-1 Antigen; D018664:Interleukin-12