A novel therapeutic vaccine of GM-CSF/TNFalpha surface-modified RM-1 cells against the orthotopic prostatic cancer.
A novel therapeutic vaccine against prostate cancer was developed by simultaneous immobilization of streptavidin-tagged bioactive GM-CSF and TNFalpha on the biotinylated surface of 30% ethanol-fixed RM-1 prostatic cancer cells. This study showed that the GM-CSF/TNFalpha-doubly surface-modified vaccine significantly extended the survival in the orthotopic model of RM-1 prostate cancer, and was superior to single GM-CSF- or TNFalpha-surface-modified vaccine. Moreover, the splenocytes from the GM-CSF/TNFalpha-vaccine-treated mice showed the most potent cytotoxicity on RM-1 cells and the highest production of RM-1-specific IFNgamma. In addition, more CD4+ and CD8+ T cells infiltrated into the tumor sites in the GM-CSF/TNFalpha-vaccine-treated mice than in the GM-CSF- or TNFalpha-vaccine-treated mice. Therefore, our study demonstrated that the efficacy of RM-1 prostate cancer cell vaccine could be improved by conjugating both GM-CSF and TNFalpha simultaneously on the surface of cancer cells, and that this modification thus has a potential translational significance.
Yin
Weihua
W
Institute of Biotherapy, School of Biotechnology, Southern Medical University, Guangzhou, China.
He
Qiushan
Q
Hu
Zhiming
Z
Chen
Zhong
Z
Qifeng
Mao
M
Zhichun
Song
S
Zhihui
Qu
Q
Xiaoxia
Nie
N
Li
Jinlong
J
Gao
Jimin
J
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D019496:Cancer Vaccines; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor