Abstract
With its vast amount of uncharacterized and characterized T cell epitopes available for activating CD4+ T helper and CD8+ cytotoxic lymphocytes simultaneously, whole tumor antigen represents an attractive alternative source of antigens as compared to tumor-derived peptides and full-length recombinant tumor proteins for dendritic cell (DC)-based immunotherapy. Unlike defined tumor-derived peptides and proteins, whole tumor lysate therapy is applicable to all patients regardless of their HLA type. DCs are essentially the master regulators of immune response, and are the most potent antigen-presenting cell population for priming and activating naïve T cells to target tumors. Because of these unique properties, numerous DC-based immunotherapies have been initiated in the clinics. In this review, we describe the different types of whole tumor antigens that we could use to pulse DCs ex vivo and in vivo. We also discuss the different routes of delivering whole tumor antigens to DCs in vivo and activating them with toll-like receptor agonists.
Highlights
Whole tumor antigen with its vast amount of characterized and uncharacterized T cell epitopes available for activating CD4+ T helper (Th) and CD8+ cytotoxic lymphocytes (CTLs) simultaneously, represents an attractive alternative source of antigens to tumor-derived peptides and full-length recombinant tumor proteins for dendritic cell (DC)-based immunotherapy [1]
Results from a meta-analysis of about 1,800 patients showed that patients who were immunized with whole tumor vaccines had a significantly higher objective response (8.1%) than patients who were immunized with defined tumor antigens (3.6%) [2]
We demonstrated that mice treated with bone marrow-derived DCs pulsed with hypochlorous acid (HOCl)-oxidized whole tumor cell lysate of ID8 expressing ovalbumin (ID8-ova) had the best tumor control with >60% cure rate [41]
Summary
Whole tumor antigen with its vast amount of characterized and uncharacterized T cell epitopes available for activating CD4+ T helper (Th) and CD8+ cytotoxic lymphocytes (CTLs) simultaneously, represents an attractive alternative source of antigens to tumor-derived peptides and full-length recombinant tumor proteins for dendritic cell (DC)-based immunotherapy [1]. The elicited immune responses in cancer patients are restricted to the peptide used for immunization and might be insufficient for controlling tumor growth. Whole tumor antigen offers this distinct advantage as it allows DCs to process and present numerous tumor antigens to stimulate a strong polyclonal T cell response to prevent tumor escape. Whole tumor cell lysate treatment is suitable for all cancer patients regardless of their HLA type. DCs are heterogeneous and different subsets of DCs could be targeted for tumor immunotherapy based on their unique toll-like receptor (TLR) expressions. We describe the different types of whole tumor antigens available for pulsing DCs ex vivo and in vivo, and we discuss the routes of administering whole tumor antigen to DCs and activating them with TLR agonists in vivo
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