Immunization with adenoviral vectors carrying recombinant IL-12 and E7 enhanced the antitumor immunity against human papillomavirus 16-associated tumor.
OBJECTIVE
Human papillomavirus (HPV) infection has a significant role in cervical carcinogenesis, and HPV oncoprotein E7 plays an important part in the formation and maintenance of cervical cancer. Interleukin-12 (IL-12) has been reported to induce a cellular immune response, and to suppress the tumor growth and the E7 production. Here we describe the use of adenoviral delivery of the HPV 16 E7 subunit (AdE7) along with adenoviral delivery of IL-12 (AdIL-12) in mice with HPV-associated tumors.


METHODS
Mice were injected with TC-1 cells to establish TC-1 tumor, and then they were immunized with AdIL-12 and/or AdE7 intratumorally. The anti tumor effects induced by AdIL-12 and/or E7 were evaluated by measuring the size of the tumor. E7-specific antibody and INF-gamma production in sera, and the T-helper cell proliferative responses were then measured. Cytotoxic T-lymphocyte (CTL) and T cell subset depletion studies were also performed.


RESULTS
Combined AdIL-12 and AdE7 infection at the tumor sites significantly enhanced the antitumor effects more than that of AdIL-12 or AdE7 single infection. This combined infection resulted in regression of the 9 mm sized tumors in 80% of animals as compare to the PBS group. E7-specific antibody and INF-gamma production in the sera, and the T-helper cell proliferative responses were significantly higher with coinfection of AdIL-12 and AdE7 than with AdIL-12 or AdE7 alone. CTL response induced by AdIL-12 and AdE7 in the coinjected group suggested that tumor suppression was mediated by mostly CD8+ and only a little by the CD4+ T cells.


CONCLUSIONS
IL-12 and E7 application using adenovirus vector showed antitumor immunity effects against TC-1 tumor, and this system could be use in clinical applications for HPV-associated cancer.
Park
Eun-Kyung
EK
Department of Obstetrics and Genecology, The Catholic University of Korea College of Medicine, Seoul, Korea.
Kim
Young-Wook
YW
Lee
Joon-Mo
JM
NamKoong
Sung-Eun
SE
Kim
Do-Gang
DG
Chun
Heung-Jae
HJ
Han
Byoung-Don
BD
Bae
Su-Mi
SM
Jin
Hyun-Sun
HS
Sin
Jeong-Im
JI
Ahn
Woong-Shick
WS