Dendritic cell-based approaches to cancer immunotherapy.
Immunologic approaches to the treatment of malignancies are currently enjoying a resurgence of enthusiasm due to the discovery of tumour-associated antigens and the requirements for stimulating a tumour antigen-specific immune response. The goal of the newer strategies is to stimulate immunity against specific tumour-associated antigens, rather than to broadly, but non-specifically, stimulate the immune system. Since dendritic cells, professional antigen-presenting cells, play a central role in stimulating immune responses in vivo, there is considerable interest in immunising patients with autologous dendritic cells loaded with tumour antigens of interest. Methods for generating large numbers of dendritic cells under clinically-applicable conditions have been developed and it has been shown that they may be loaded with antigen in many different forms including proteins or peptides, RNA or DNA and cellular extracts. Ongoing research is seeking to optimise the purity, antigen loading and maturation of the dendritic cells. Phase I clinical trials have been initiated in order to study the safety and feasibility of immunisations with dendritic cells in humans with various malignancies. Phase II studies will be performed to establish which tumours and clinical scenarios will be most relevant for dendritic cell immunotherapy. Although the commercial applicability of dendritic cell-based immunotherapy has been recognised by the biotechnology industry, commercial availability of dendritic cell vaccines await phase III studies.
Department of Medicine, Duke University Medical Center, Box 2606, Durham, NC 27710, USA. morse004@mc.duke.edu
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