Enhancing therapy of B16F10 melanoma efficacy through tumor vaccine expressing GPI-anchored IL-21 and secreting GM-CSF in mouse model.
In the present study, we developed the tumor vaccine expressing IL-21 in the GPI-anchored form together with secreting GM-CSFs and investigated its antitumor efficacy in C57BL/6 mouse model. The fusion genes containing IL-21 and the GPI anchor signal sequence were acquired by overlaping PCR, inserted into the downstream of two multi-clone sites in recombinant plasmid pRSC/GM-CSFs to form pRSC/IL-21-gpi-GM-CSFs that was transfected into the B16F10 cells. The tumor cell vaccine B16F10/IL-21-gpi-GM-CSFs was identified by reverse transcription PCR, IFA and FCM, respectively. The results showed that the pRSC/IL-21-gpi-GM-CSFs had no cell cycle and proliferative state impact on the B16F10 cells after transfected, and that the tumor vaccine B16F10/IL-21-gpi-GM-CSFs increased the cytotoxicities of NK cells and CD8(+)CTL, enhanced the level of serum IFN-gamma, augmented therapy of tumor effect and prolonged survival time in the tumor-bearing mice immunized with the tumor vaccine B16F10/IL-21-gpi-GM-CSFs. The data that we presented here provided a rationale and practical platform for clinical testing of enhancing cell therapy of B16F10 melanoma efficacy by modified tumor vaccine expressing GPI-anchored IL-21 and secreting GM-CSF.
Zhao
Fengshu
F
Department of Pathogenic Biology and Immunology, Medical College, Southeast University, #87 Dingjiaqiao Rd., Jiangsu Province, Nanjing 210009, China.
Dou
Jun
J
He
Xiang Feng
XF
Wang
Jing
J
Chu
Lili
L
Hu
Weihua
W
Yu
Fangliu
F
Hu
Kai
K
Wu
Yun
Y
Gu
Ning
N
D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D007155:Immunologic Factors / Q000096:biosynthesis* / Q000235:genetics; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000097:blood; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D000098546:Interleukin-21
D019496:Cancer Vaccines; D007155:Immunologic Factors; D007378:Interleukins; D019444:Vaccines, DNA; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000098546:Interleukin-21