More than chemotaxis: a new anti-tumor DC vaccine modified by rAAV2-SLC.
Secondary lymphoid tissue chemokine (SLC) is strongly expressed in secondary lymphoid organs. Its ability to facilitate chemotaxis of both dendritic cells (DC) and T cells makes it a promising candidate for cancer therapy. In this study, we modified a BMDC vaccine by incorporating the SLC mature peptide gene. The efficacy of this vaccine was evaluated using a mouse hepatocellular carcinoma (HCC) model, with rAAV2 as the gene delivery vector. The rAAV2 encoding SLC (rAAV2-SLC) transfected immature BMDCs at high efficiency and the anti-tumor effects of SLC gene modified BMDCs (rAAV2-SLC/BMDC) were evaluated. In addition, rAAV2-SLC/BMDC vaccine injected directly into tumors attracted more CD4(+) and CD8(+) T lymphocytes into tumors and showed stronger anti-tumor effects than footpad delivery. Moreover, we found that the phenotypic expression of MHC II, the secretion of IL-12 and IFN-gamma, and T cell stimulation were increased in vitro following treatment with rAAV2-SLC/BMDC vaccine and these responses were inhibited by PTX. In vivo, PTX also inhibited the anti-tumor effects of the vaccine. The results suggest that the expression of SLC by rAAV2-SLC/BMDC plays more than a chemotactic role in anti-tumor responses, thus these studies further demonstrate that SLC has potential to be valuable in cancer therapy.
Liang
Chun-min
CM
Department of Anatomy and Histology & Embryology, Shanghai Medical College Fudan University, 138 Yi Xue Yuan Road, 200032 Shanghai, PR China.
Ye
Sheng-long
SL
Zhong
Cui-ping
CP
Zheng
Ning
N
Bian
Wei
W
Sun
Rui-xia
RX
Chen
Jun
J
Li
Ri-lun
RL
Zhou
Shuang
S
Liu
Yin-kun
YK
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000276:immunology*; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D000229:Dependovirus / Q000235:genetics*; D005260:Female; D008114:Liver Neoplasms, Experimental / Q000517:prevention & control*; D051379:Mice; D008819:Mice, Nude; D037342:Pertussis Toxin / Q000494:pharmacology; D014161:Transduction, Genetic; D014162:Transfection
D019496:Cancer Vaccines; C515479:Ccl21c protein, mouse; D054421:Chemokine CCL21; D019742:Chemokines, CC; D037342:Pertussis Toxin