Mannan-modified adenovirus as a vaccine to induce antitumor immunity.
Tumor vaccine is a useful strategy for cancer therapy. However, priming of the immune system requires the relevant antigen to be presented by antigen-presenting cells (APCs). Here, we employed telomerase reverse transcriptase as a model antigen to explore the feasibility of using mannan-modified adenovirus as a tumor vaccine. We found that tumor immunogene therapy with the vaccine was effective at protective antitumor immunity in mice. The antigen-specific cytotoxic T lymphocytes were found in in vitro cytotoxicity assay. The elevation of the killing activity could be abrogated by anti-CD8 or anti-major histocompatibility complex-I antibodies. Adoptive transfer of purified CD8+ cells, and CD4+ cells to a less extent, was effective at antitumor activity. In vivo antitumor activity could be abrogated by depleting CD4+ T lymphocytes. A possible explanation for the antitumor effects may be the antigen was transferred to APCs in the presence of mannan. These observations provide insights into the design of novel vaccine strategies and might be important for the future application of antigens identified in other diseases.
Ding
Z-Y
ZY
Department of Oncology, National Key Laboratory of Biotherapy, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Sichuan, The People's Republic of China.
Wu
Y
Y
Luo
Y
Y
Su
J-M
JM
Li
Q
Q
Zhang
X-W
XW
Liu
J-Y
JY
He
Q-M
QM
Yang
L
L
Tian
L
L
Zhao
X
X
Deng
H-X
HX
Wen
Y-J
YJ
Li
J
J
Kang
B
B
Wei
Y-Q
YQ
D000256:Adenoviridae / Q000235:genetics*; D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D008212:Lymphocyte Depletion; D008351:Mannans / Q000235:genetics* / Q000378:metabolism; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D008351:Mannans