Combination of treatment with death receptor 5-specific antibody with therapeutic HPV DNA vaccination generates enhanced therapeutic anti-tumor effects.
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.
Tseng
Chih Wen
CW
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Monie
Archana
A
Trimble
Cornelia
C
Alvarez
Ronald D
RD
Huh
Warner K
WK
Buchsbaum
Donald J
DJ
Straughn
J Michael
JM
Wang
Mei-Cheng
MC
Yagita
Hideo
H
Hung
Chien-Fu
CF
Wu
T-C
TC
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*
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