title: 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.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Chih Wen
authors.initials: CW
authors.lastname: Tseng
authors.forename: Archana
authors.initials: A
authors.lastname: Monie
authors.forename: Cornelia
authors.initials: C
authors.lastname: Trimble
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Alvarez
authors.forename: Warner K
authors.initials: WK
authors.lastname: Huh
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Buchsbaum
authors.forename: J Michael
authors.initials: JM
authors.lastname: Straughn
authors.forename: Mei-Cheng
authors.initials: MC
authors.lastname: Wang
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Chien-Fu
authors.initials: CF
authors.lastname: Hung
authors.forename: T-C
authors.initials: TC
authors.lastname: Wu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D037282:Calreticulin / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D005260:Female; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000628:therapy*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000037:antagonists & inhibitors* / Q000276:immunology; D013154:Spleen / Q000276:immunology; D016019:Survival Analysis; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D037282:Calreticulin; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D019444:Vaccines, DNA; C059731:oncogene protein E7, Human papillomavirus type 16; D007371:Interferon-gamma