Immunization with adenoviral vectors carrying recombinant IL-12 and E7 enhanced the antitumor immunity to human papillomavirus 16-associated tumor
| Autor: | Eun Kyung Park, Su-Mi Bae, Joon-Mo Lee, Woong-Shick Ahn, Heung-Jae Jun, Hyun-Sun Jin, Byoung-Don Han, Do-Gang Kim, Young Joo Lee, S. E. Namkoong |
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| Rok vydání: | 2004 |
| Předmět: |
CD4-Positive T-Lymphocytes
Lung Neoplasms Papillomavirus E7 Proteins Uterine Cervical Neoplasms CD8-Positive T-Lymphocytes medicine.disease_cause Transfection Adenoviridae Mice Immune system Cell Line Tumor medicine Cytotoxic T cell Animals Humans Cervix neoplasm biology business.industry Obstetrics and Gynecology Oncogene Proteins Viral Interleukin-12 Recombinant Proteins Mice Inbred C57BL CTL Oncology Immunoglobulin G Immunology Interleukin 12 biology.protein Female Antibody business CD8 T-Lymphocytes Cytotoxic |
| Zdroj: | Gynecologic oncology. 97(2) |
| ISSN: | 0090-8258 |
| Popis: | Objective Human papillomavirus (HPV) infection play a significant role in cervical carcinogenesis, and HPV oncoprotein E7 has important functions in the formation and maintenance of cervical cancers. Interleukin-12 (IL-12) has been reported to induce cellular immune responses, and has also been demonstrated to suppress the growth of tumors and the expression of E7. Here, we investigate the utility of adenovirus E7 (AdE7) and adenovirus IL-12 (AdIL-12) for protection against TC-1 tumor using an animal model. Methods The antitumor effects induced by AdIL-12 and/or E7 were assessed by measurements of tumor size. E7-specific antibody and INF-γ production in sera were measured, as were T-helper cell proliferative responses. Cytotoxic T-lymphocytes (CTL) and T cell subset depletion studies were also performed. Results Infection of tumor sites with a combination of AdIL-12 and AdE7 resulted in an antitumor effect which was significantly more profound than that which resulted from singular infections with either AdIL-12 or AdE7. Combined infection resulted in regression of 9-mm-sized tumors in ∼80% of our experimental animals as compared to the PBS group. Serum levels of E7-specific antibody and INF-γ production, as well as T-helper cell proliferative responses, were found to be significantly higher in coinfected with AdIL-12 and AdE7 group than in single infection with either AdIL-12 or AdE7 group. CTL responses only exhibited by the AdIL-12 and AdE7 coinjected group suggested that these tumor suppression effects were mediated primarily by CD8+ and, to a lesser degree, by CD4+ T cells. Conclusion Combined injection with adenovirus carrying IL-12 and E7 induced significant antitumor immunity against TC-1 tumors. They may prove useful in clinical applications for the treatment of HPV-associated tumors. |
| Databáze: | OpenAIRE |
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