Immunotherapy of tumors with recombinant adenovirus encoding macrophage inflammatory protein 3beta induces tumor-specific immune response in immunocompetent tumor-bearing mice.
OBJECTIVE
Tumor immunotherapy aims at activating the body's own immune system to fight an existing tumor. Effective antitumor responses require tumor antigens to be presented to lymphocytes. We aimed to test the hypothesis that intratumoral administration of recombinant adenovirus encoding MIP3beta would induce antitumor immunity by attracting and facilitating the interaction between lymphocytes and dendritic cells.


METHODS
A recombinant adenovirus encoding microphage inflammatory protein 3beta (AdMIP3beta) was constructed. The antitumor activity of AdMIP3beta in BALB/c and C57BL/6 mice bearing CT26 colon adenocarcinoma and Lewis lung cancer was evaluated.


RESULTS
Immunotherapy with AdMIP3beta resulted in significant inhibition of tumor growth and prolonged survival of tumor-bearing mice. Tumor-specific immune responses elicited by AdMIP3beta include MHC class I-dependent CD8(+) CTL-mediated immune response and IFN-gamma response. Immunohistochemical staining demonstrated numerous CD11c(+) cells and CD3(+) T lymphocytes within tumor tissues of AdMIP3beta-treated mice. These findings suggest that the mechanism of specific antitumor immunity induced by AdMIP3beta may be involved in the chemoattraction of both T lymphocytes and DCs to the tumor site and thus facilitate the process of antigen capture and mature DC to prime naive T cells.


CONCLUSIONS
The present study may be important in the exploration of the potential application of AdMIP3beta in the treatment of a broad spectrum of tumors.
Hou
Jian-mei
JM
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
Zhao
Xia
X
Tian
Ling
L
Li
Gang
G
Zhang
Ru
R
Yao
Bing
B
Deng
Hong-xin
HX
Yang
Jin-liang
JL
Wei
Yu-quan
YQ
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism*; D019264:Adoptive Transfer; D000818:Animals; D054415:Chemokine CCL19 / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D007107:Immune System / Q000502:physiology*; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D011897:Random Allocation; D013601:T-Lymphocytes / Q000276:immunology
D054415:Chemokine CCL19; D007371:Interferon-gamma