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Prof. Yong Taik LIM developed a Techonology for Enhancing Dendritic Cell-based Cancer Immunotherapy 2016.12.12
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In recent preclinical and clinical studies, the efficacy of dendritic cells (DCs)-based immunotherapy has been limited by the lack of efficient antigen loading, maturation and poor migration rate toward lymph node of DCs. The well-designed activation of DCs by enhancing the delivery of antigens and immunostimulatory adjuvants into DCs is a key strategy for efficient cancer immunotherapy. Antigen-antibody immune complexes (ICs) are known to directly bind to and crosslink Fc-gamma receptors (FcγRs) on DCs, which induced enhanced migration of DCs to draining lymph nodes through the up-regulation of the chemokine receptor CCR7 and cross-presentation, inducing cytotoxic T lymphocyte (CTL) response against tumor antigen. Thus, the targeting of FcγR will be a promising strategy for vaccine design and generating efficient DC-based immunotherapy of tumors.

 

Recently, Prof. Yong Taik Lim’s group at Sungkyunkwan University reported that a novel nanotechnology platform that can overcome the current limitation of DCs-based cancer immunotherapy has been developed. In his group, ICs mimicking synthetic vaccine nanoparticles (NPs) were designed and successfully synthesized by the coating of poly (lactic-co-glycolic acid) (PLGA) NPs containing adjuvant (CpG ODNs as TLR9 ligands) with OVA proteins (as model antigens), and by the formation of OVA-OVA antibody ICs. They also demonstrated that ICs mimicking synthetic vaccine NPs induced the effective delivery of antigen and adjuvant to DCs, which could induce powerful T cell-based immune responses and enhanced anti-tumor immunity, by the combination of FcγR-mediated enhanced uptake and immunostimulatory effect of adjuvant. Moreover, ICs mimicking synthetic vaccine NPs also stimulated DC migration toward the lymph node, which could be an alternative strategy to resolve the current limitation of DC-based immunotherapy. 

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