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Preparation of Tumor Antigen-loaded Mature Dendritic Cells for Immunotherapy
Published on: August 1, 2013
Dendritic cells in cancer immunotherapy
1Departments of Pathology and Medicine, Stanford University School of Medicine, Palo Alto, California 94304, USA. lfong@stanford.edu
The potential to harness the potency and specificity of the immune system underlies the growing interest in cancer immunotherapy. One such approach uses bone marrow-derived dendritic cells, phenotypically distinct and extremely potent antigen-presenting cells, to present tumor-associated antigens and thereby generate tumor-specific immunity. Support for this strategy comes from animal studies that have demonstrated that dendritic cells, when loaded ex vivo with tumor antigens and administered to tumor-bearing hosts, can elicit T cell-mediated tumor destruction. These observations have led to clinical trials designed to investigate the immunologic and clinical effects of antigen-loaded dendritic cells administered as a therapeutic vaccine to patients with cancer. In the design and conduct of such trials, important considerations include antigen selection, methods for introducing the antigen into MHC class I and II processing pathways, methods for isolating and activating dendritic cells, and route of administration. Although current dendritic cell-based vaccination methods are cumbersome, promising results from clinical trials in patients with malignant lymphoma, melanoma, and prostate cancer suggest that immunotherapeutic strategies that take advantage of the antigen presenting properties of dendritic cells may ultimately prove both efficacious and widely applicable to human tumors.
The potential to harness the potency and specificity of the immune system underlies the growing interest in cancer immunotherapy. One such approach uses bone marrow-derived dendritic cells, phenotypically distinct and extremely potent antigen-presenting cells, to present tumor-associated antigens and thereby generate tumor-specific immunity. Support for this strategy comes from animal studies that have demonstrated that dendritic cells, when loaded ex vivo with tumor antigens and administered to tumor-bearing hosts, can elicit T cell-mediated tumor destruction. These observations have led to clinical trials designed to investigate the immunologic and clinical effects of antigen-loaded dendritic cells administered as a therapeutic vaccine to patients with cancer. In the design and conduct of such trials, important considerations include antigen selection, methods for introducing the antigen into MHC class I and II processing pathways, methods for isolating and activating dendritic cells, and route of administration. Although current dendritic cell-based vaccination methods are cumbersome, promising results from clinical trials in patients with malignant lymphoma, melanoma, and prostate cancer suggest that immunotherapeutic strategies that take advantage of the antigen presenting properties of dendritic cells may ultimately prove both efficacious and widely applicable to human tumors.
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