Dendritic cell fusion vaccines for cancer immunotherapy

Abstract

The use of tumour vaccines is being explored as a means of generating effective antitumour immune responses in patients with cancer. Dendritic cells (DCs) are the most potent antigen-presenting cells that are essential for initiating primary immune responses. As such, DCs are being studied as a platform for the design of cancer vaccines. DCs loaded with tumour antigens or whole tumour cell derivatives stimulate tumour-specific immunity. A promising vaccine strategy involves the fusion of DCs with whole tumour cells. DC/tumour fusions express a broad array of tumour antigens, including those yet to be identified, in the context of DC-mediated costimulation. Animal models have demonstrated that vaccination with fusion cells is protective against tumour challenge and results in the regression of established metastatic disease. In vitro human studies have demonstrated that DC/tumour fusions potently stimulate antitumour immunity and lysis of autologous tumour cells. Vaccination of cancer patients with DC/tumour fusions is being studied in Phase I/II clinical trials. Preliminary results demonstrate that generation of a vaccine is feasible and that vaccination is associated with minimal toxicity. Immunological and clinical responses have been found in a subset of patients.