Combination of treatment with death receptor 5-specific antibody with therapeutic HPV DNA vaccination generates enhanced therapeutic anti-tumor effects.

Abstract

There is currently a vital need for the development of novel therapeutic strategies for the control of advanced stage cancers. Antigen-specific immunotherapy and the employment of antibodies against the death receptor 5 (DR5) have emerged as two potentially promising strategies for cancer treatment. In the current study, we hypothesize that the combination of treatment with the anti-DR5 monoclonal antibody, MD5-1 with a DNA vaccine encoding calreticulin (CRT) linked to human papillomavirus type 16 (HPV-16) E7 antigen (CRT/E7(detox)) administered via gene gun would lead to further enhancement of E7-specific immune responses as well as anti-tumor effects. Our results indicated that mice bearing the E7-expressing tumor, TC-1 treated with MD5-1 monoclonal antibody followed by CRT/E7(detox) DNA vaccination generated the most potent therapeutic anti-tumor effects as well as highest levels of E7-specific CD8+ T cells among all the groups tested. In addition, treatment with MD5-1 monoclonal antibody was capable of rendering the TC-1 tumor cells more susceptible to lysis by E7-specific cytotoxic T lymphocytes. Our findings serve as an important foundation for future clinical translation.

• Authors: Chih Wen Tseng, Archana Monie, Cornelia Trimble, Ronald D Alvarez, Warner K Huh, Donald J Buchsbaum, J Michael Straughn Jr, Mei-Cheng Wang, Hideo Yagita, Chien-Fu Hung, T-C Wu
• Journal: Vaccine (Vaccine) Vol. 26 Issue 34 Pg. 4314-9 (Aug 12 2008) ISSN: 0264-410X [Print] Netherlands
• PMID: 18598733 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Calreticulin
• Oncogene Proteins, Viral
• Papillomavirus E7 Proteins
• Papillomavirus Vaccines
• Receptors, TNF-Related Apoptosis-Inducing Ligand
• Vaccines, DNA
• oncogene protein E7, Human papillomavirus type 16
• Interferon-gamma

Topics

• Animals
• Antibodies, Monoclonal (therapeutic use)
• CD8-Positive T-Lymphocytes (immunology)
• Calreticulin (genetics, immunology)
• Cell Line, Tumor
• Female
• Immunotherapy (methods)
• Interferon-gamma (biosynthesis)
• Mice
• Mice, Inbred C57BL
• Neoplasms (therapy)
• Oncogene Proteins, Viral (genetics, immunology)
• Papillomavirus E7 Proteins
• Papillomavirus Vaccines (genetics, immunology, therapeutic use)
• Receptors, TNF-Related Apoptosis-Inducing Ligand (antagonists & inhibitors, immunology)
• Spleen (immunology)
• Survival Analysis
• Vaccines, DNA (genetics, immunology, therapeutic use)