1. ¹Research Unit, Saskatchewan Cancer Agency, Department of Oncology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
2. ²Research Unit, Saskatchewan Cancer Agency, Department of Immunology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
3. ³Research Unit, Saskatchewan Cancer Agency, Department of Pathology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
4. ⁴Gene Therapy Branch, National Institute of Dental Research, National Institute of Health, Bethesda, MD, USA

Correspondence: Dr J Xiang, Research Unit, Saskatchewan Cancer Agency, Department of Oncology, University of Saskatchewan, 20 Campus Drive, Saskatoon, Saskatchewan S7N 4H4, Canada. E-mail: jxiang@scf.sk.ca

Received 13 December 2005; Revised 15 August 2006; Accepted 9 October 2006; Published online 19 January 2007.

Abstract

The dual role of heat shock protein 70 (HSP70), as antigenic peptide chaperone and danger signal, makes it especially important in dendritic cell (DC)-based vaccination. In this study, we investigated the impacts of apoptotic transgenic MCA/HSP tumor cells expressing HSP70 on DC maturation, T-cell stimulation and vaccine efficacy. We found that DCs with phagocytosis of MCA/HSP in early phase of apoptosis expressed more pMHC I complexes, stimulated stronger cytotoxic T lymphocyte (CTL) responses (40% specific killing at an E:T cell ratio of 50) and induced immune protection in 90% of mice against MCA tumor cell challenge, compared with 25% specific CTL killing activity and 60% immune protection seen in mice immunized with DC with phagocytosis of MCA/HSP in late phase of apoptosis (P<0.05). Similar results were confirmed in another EG7 tumor model also expressing HSP70. Taken together, our data demonstrate that HSP70 on apoptotic tumor cells stimulate DC maturation, and DC with phagocytosis of apoptotic tumor cells expressing HSP70 in early phase of apoptosis more efficiently induced tumor-specific CTL responses and immunity than DCs with phagocytosis of apoptotic tumor cells in late phase of apoptosis. These results may have an important impact in designing DC-based antitumor vaccines.