1. ¹Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
2. ²Department of Anatomy, Chung-Ang University College of Medicine, Dongjak-Gu, Seoul, South Korea
3. ³Department of Biostatistics, Johns Hopkins Medical Institutions, Baltimore, MD, USA
4. ⁴Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
5. ⁵Department of Obstetrics and Gynecology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
6. ⁶Department of Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

Correspondence: Dr T-C Wu, Department of Pathology, Johns Hopkins University School of Medicine, CRB II Room 309, 1550 Orleans Street, Baltimore, MD 21231, USA. E-mail: wutc@jhmi.edu

Received 13 February 2008; Revised 19 March 2008; Accepted 26 March 2008; Published online 8 May 2008.

Abstract

Multimodality treatments that combine conventional cancer therapies with antigen-specific immunotherapy have emerged as promising approaches for the control of cancer. In the current study, we have explored the effect of doxorubicin on the antigen-specific immune responses generated in mice vaccinated with calreticulin (CRT)/E6 and/or Ii-PADRE DNA. We observed that pretreatment with doxorubicin suppressed the E6-specific CD8⁺ T-cell immune responses generated by CRT/E6 DNA vaccination in vaccinated mice. In contrast, pretreatment with doxorubicin enhanced the PADRE-specific CD4⁺ T-cell immune responses generated by Ii-PADRE DNA vaccination. Furthermore, coadministration of Ii-PADRE DNA could not only reverse the suppression, but also enhanced the E6-specific CD8⁺ T-cell responses in CRT/E6-vaccinated mice pretreated with doxorubicin. Finally, treatment with doxorubicin followed by CRT/E6 combined with Ii-PADRE DNA vaccination led to enhanced antitumor effects and prolonged survival in TC-1 tumor-bearing mice. The clinical implications of the current study are discussed.