Transfection of IL-2 and/or IL-12 genes into spleen in treatment of rat liver cancer.
OBJECTIVE
To test the efficacy of gene therapy in rat liver tumor.


METHODS
A retroviral vector GCIL12EIL2PN encoding human IL-2 (hIL-2) and mouse IL-12 (mIL-12) fused gene and its packaging cell were constructed. The packaging cell lines contained of IL-2 and/or IL-12 genes were injected intrasplenically to transfect splenocyte at different time. The therapeutic effect, immune function and toxic effect were evaluated.


RESULTS
The average survival times of the 4 groups using IL genes at days 1, 3, 5 and 7 after tumor implantation were 53.3+/-3.7, 49.3+/-4.2, 31.0+/-2.1 and 24.3+/-1.4 d respectively in IL-2/IL-12 fused gene group, 25.0+/-2.5, 23.5+/-2.0, 18.3+/-2.4 and 12.0+/-1.8 d respectively in IL-2 gene treatment group, and 39.0+/-4.8, 32.0+/-3.9, 23.0+/-2.5 and 19.4+/-2.1 d respectively in IL-12 gene treatment group (P<0.01, n=10). In the IL-12/IL-2 fused gene treatment group, 30% of rats treated at days 1 and 3 survived more than 60 d and serum mIL-12 and hIL-2 levels were still high at day 3 after treatment. Compared with IL alone, NK cell activity was strongly stimulated by IL-2/IL-12 gene. Microscopy showed that livers were infiltrated by a number of lymphocytes.


CONCLUSIONS
IL-2 and/or IL-12 genes injected directly into spleen increase serum IL-2 and IL-12 levels and enhance the NK cell activity, which may inhibit the liver tumor growth. The therapy of fused gene IL-2/IL-12 is of low toxicity and relatively high NK cell activity. Our data suggest that IL-2/IL-12 fused gene may be a safe and efficient gene therapy for liver tumor. The gene therapy should be administrated as early as possible.
You
Tian-Geng
TG
Department of Comprehensive Treatment III, Eastern Hepatobiliary Hospital, Second Military Medical University, Changhai Road 225, Shanghai 200433, China.
Wang
Hong-Shun
HS
Yang
Jia-He
JH
Qian
Qi-Jun
QJ
Fan
Rui-Fang
RF
Wu
Meng-Chao
MC
D000276:Adjuvants, Immunologic / Q000235:genetics*; D000818:Animals; D000970:Antineoplastic Agents; D019677:Artificial Gene Fusion; D005822:Genetic Vectors; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics*; D007376:Interleukin-2 / Q000235:genetics*; D008113:Liver Neoplasms / Q000628:therapy*; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D012190:Retroviridae / Q000235:genetics; D013154:Spleen; D014162:Transfection
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D007376:Interleukin-2; D018664:Interleukin-12