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

Chih Wen Tseng, Archana Monie, Cornelia Trimble, Ronald D. Alvarez, Warner K. Huh, Donald J. Buchsbaum, J. Michael Straughn, Mei Cheng Wang, Hideo Yagita, Chien Fu Hung, T. C. Wu

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)4314-4319
Number of pages6
JournalVaccine
Volume26
Issue number34
DOIs
StatePublished - Aug 12 2008

Keywords

  • Anti-DR5 antibody
  • Calreticulin (CRT)
  • DNA vaccine
  • E7
  • Human papillomavirus (HPV)

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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