Immunogenicity of Dendritic-Tumor Fusion Hybrids and Their Utility in Cancer Immunotherapy

Abstract

Cancer immunotherapy using fusion hybrid cells generated from dendritic cells (DCs) and tumor cells may be more effective than other DC-based vaccines. DC-tumor fusion potentially confers not only the DCs' antigen-presenting functionality but also a continuing source of endogenous tumor antigens for major-histocompatibility-complex-restricted T-cell sensitization. In animal models, many investigators demonstrated that vaccination with fusion hybrids was protective against tumor challenge and therapeutic, resulting in the regression of established tumors. In clinical trials for patients with a variety of metastatic diseases, fusion hybrid vaccines were well tolerated, but the overall objective response rate was only 10.9%. Careful scrutiny of a large number of publications revealed that, in most cases, no definitive evidence of heterokaryonic fusion cell formation was found. Further corroboration of this conclusion comes from reports that fusion hybrids generated from autologous (syngeneic) and allogeneic DCs displayed equivalent immunological function and therapeutic effects in vitro and in vivo. This puzzling finding suggests that effective fusion immunotherapy depends on tumor antigen scavenging and presentation by antigen-presenting cells (APCs) of host origin and is in violation of the basic tenet of the principle of DC function. We believe that conclusions drawn from reported clinical trials have not properly evaluated the efficacy of the DC-tumor hybrid vaccine, and therefore, they neither confirm nor disclaim the potential benefits that may be derived from this form of immunotherapy.