This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Objective: Dendritic cells (DCs) are the most potent of the antigen presenting cells (APCs) and play a key role in initiating and directing primary immune responses. As a result, DC-based immunotherapies have been considered as highly promising treatment modalities for both cancer and HIV-infected patients. Encouraged by the results from animal models, researchers have conducted or initiated more than 100 cancer immunotherapy clinical trials using different approaches. Although some approaches are showing signs of promise, it is clear that the next generation of DC vaccines needs to be further optimized to achieve better and more consistent therapeutic efficacy. The rhesus macaque model provides a unique system in which the DC vaccine protocols currently used in clinical trials can be recapitulated. Our long-term goal is to take the advantage of the monkey model to accelerate the improvement of DC vaccines. In this project, we will test a novel strategy to improve DC vaccines. We hypothesize that inhibition of endogenous interleukin 10 activity can enhance the potency of DC vaccines to induce adaptive immunity in vivo. More importantly, the accomplishment of this project will establish a foundation that enables us to evaluate various DC vaccine strategies in the animal model that closely approximates the human conditions.
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