[Application of fusion gene mGM-CSF/hIL-2 to specific immunotherapy induced by hepatic tumor cell vaccine].
OBJECTIVE
Surgical resection is the main treatment for primary liver cancer, but there is no ideal treatment for postoperative recurrence and metastasis. Recently, due to the development of immunology, immunotherapy is regarded as a promising treatment for hepatoma. This study was to prepare H22 hepatoma tumor vaccine modified by the fusion gene of mouse granulocyte-monocyte colony stimulating factor (mGM-CSF) and human interleukin-2 (hIL-2), and explore its specific antitumor immunity.


METHODS
Eukaryotic vector expressing fusion gene mGM-CSF/hIL-2 was transfected into H22 cells to establish tumor vaccine (H22/GM-CSF/IL-2) and inoculate mice; pcDNA3.1 was also transfected into H22 cells as empty control (H22/neo). Tumor-bearing mouse models were established. The cytotoxicities of the splenocytes from the mice in H22/GM-CSF/IL-2, H22/neo, and blank control groups were examined by 51Cr release assay. The serum levels of interleukin-10 (IL-10), interferon-gamma (IFN-gamma) were detected by ELISA. The survival of mice was observed.


RESULTS
H22 cell vaccine modified by mGM-CSF/hIL-2 was successfully established. The killing rate of H22 cells by splenocytes was significantly higher in H22/GM-CSF/IL-2 group than in H22/neo and blank control groups (38.3% vs. 13.6% and 7.5%, P<0.05). The serum level of IFN-gamma was significantly higher and the serum level of IL-2 was significantly lower in H22/GM-CSF/IL-2 group than in H22/neo group [(12.83+/-0.75) pg/mL vs. (7.83+/-0.65) pg/mL, P<0.01; (4.58+/-0.34) pg/ml vs. (8.15+/-0.28) pg/mL, P<0.01]. The survival time of mice was significantly longer in H22/GM-CSF/IL-2 group than in H22/neo and blank control groups [(40+/-6) days vs. (30+/-3) days and (19+/-4) days, P<0.01].


CONCLUSIONS
Transfecting fusion gene mGM-CSF/hIL-2 into the novel autologous tumor vaccine H22 can elicit specific cellular immune response and improve the host's antitumor immune response, and prolong the survival of tumor-bearing mice.
Yang
Wei
W
Department of Hepatobiliary Surgery, The First Affiliated Hospital, Xioan Jiaotong University, Xioan, Shaanxi, 710061, P. R. China. joneso297@sina.com
Guo
Cheng
C
Liu
Qing-Guang
QG
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D050939:Gene Fusion; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D007376:Interleukin-2 / Q000235:genetics*; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C
D019496:Cancer Vaccines; D007376:Interleukin-2; D016753:Interleukin-10; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor