Induction of an effective anti-tumor immune response and tumor regression by combined administration of IL-18 and Apoptin.
Immunization strategies using plasmid DNA can potentially improve humoral and cellular immune responses that protect against cancer and infectious diseases. The chicken anemia virus-derived Apoptin protein exhibits remarkable specificity in its ability to induce apoptosis in tumor cells, but not in normal diploid cells. Interleukin-18 (IL-18) is a Th1-type cytokine that has demonstrated potential as a biological adjuvant in murine tumor models. In this study, we analyzed the anti-tumor potential and mechanism of action of simultaneous Apoptin and IL-18 gene transfer in C57BL/6 mice bearing Lewis lung carcinoma (LLC). Here we report that the growth of established tumors in mice immunized with pAPOPTIN in conjunction with pIL-18 was significantly inhibited compared with the growth of tumors in mice immunized with the empty vector (EV) or pAPOPTIN alone. Furthermore, the immunization of mice with pAPOPTIN in conjunction with pIL-18 elicited strong natural killer activity and LLC tumor-specific cytotoxic T lymphocyte (CTL) responses in vitro. In addition, T cells from lymph nodes of mice vaccinated with pIL-18 or pAPOPTIN + pIL-18 secreted high levels of the Th1 cytokine IL-2 and IFN-gamma, indicating that the regression of tumor cells is related to a Th1-type dominant immune response. These results demonstrate that vaccination with Apoptin together with IL-18 may be a novel and powerful strategy for cancer immunotherapy.
Lian
Hai
H
Genetic Engineering Laboratory, Academy of Military Medical Sciences, 1068 Qinglong Road, Changchun, Jilin 130062, People's Republic of China.
Jin
Ningyi
N
Li
Xiao
X
Mi
Zhiqiang
Z
Zhang
Jingmin
J
Sun
Lili
L
Li
Xuemei
X
Zheng
Hongling
H
Li
Ping
P
D000818:Animals; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000628:therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
D036022:Capsid Proteins; D020382:Interleukin-18; C091717:VP3 protein, Chicken anemia virus