RNA-transfected dendritic cells in cancer immunotherapy.

Abstract

The field of cancer immunotherapy has been recently invigorated by the discovery that vaccination with dendritic cells (DCs) pulsed with tumor antigens is a potent strategy to elicit protective immunity in tumor-bearing animals. The recognition that the cellular arm of the immune response is best equipped to recognize tumor cells as foreign and to lead to their eradication has shifted the emphasis in vaccine development. Vaccines that induce cellular responses, especially by the CD8+ cytotoxic T lymphocyte (CTL) arm of the immune system, are now favored over those that activate humoral immunity. At the same time, DCs have emerged as the most potent antigen-presenting cells (APCs) for eliciting antitumor CTLs. DCs can be generated from cancer patients by culturing adherent PBMCs from the patients for 5–7 days in the presence of cytokines (1). The major research effort in many labs involves the choice of tumor antigen with which to load these DCs. The issues being addressed are, first, the composition of the antigen, whether a defined tumor antigen or an unfractionated mixture of tumor-derived antigens; and second, the form in which the antigen should be presented, whether as a polypeptide or a nucleic acid. Here, we focus on the use of RNA-transfected DCs in cancer immunotherapy, reviewing current data on the transfection of DCs with RNAs encoding either defined or unfractionated tumor antigens. We also consider the advantages and disadvantages of employing RNA transfection in loading DCs with tumor antigens and the merits of RNA transfection in situations where a low level of transiently expressed protein is sufficient to allow antigen presentation.