An effective cancer vaccine modality: Lentiviral modification of dendritic cells expressing multiple cancer-specific antigens

Abstract

Viral modification of dendritic cells (DCs) may deliver a "danger signal" critical to the hypo-reactive DCs in cancer patients. Using three highly differentially expressed hepatoma tumor-associated antigens (TAAs): stem cell antigen-2 (Sca-2), glycoprotein 38 (GP38) and cellular retinoic acid binding protein 1 (RABP1), we explored the therapeutic potential of the DCs modified with lentiviral vectors (LVs). Preventive and therapeutic injection of the LV-TAA-DC vaccine into tumor-bearing mice elicited a strong anti-tumor response and extended survival, which was associated with tumor-specific interferon-γ and cytotoxic T cell responses. In vivo elimination of the LV-TAA-DCs by a co-expressed thymidine kinase suicide gene abrogated the therapeutic effect. The modification of DCs with LVs encoding multiple TAAs offers a great opportunity in cancer immunotherapy. © 2006 Elsevier Ltd. All rights reserved.