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Prof. Yong Taik LIM Develops Implantation of Synthetic Immune Niche that Prevents Tumor Recurrance 2018.04.11
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Cancer vaccines are an attractive option for improving disease-free survival following surgical resection of solid tumors. However, several clinical studies have shown that while cancer vaccines can routinely induce protection in a prophylactic model, the same vaccines often show only limited therapeutic efficacy. The tumor immunosuppressive network, formed by interactions between cancer cells and host immune cells, is a major obstacle to achieving complete tumor eradication. Myeloid-derived suppressor cells (MDSCs) can be considered critical players in tumor-induced immunosuppression in both animal models and cancer patients, which they have a remarkable ability to suppress the activation and proliferation of T cells. Therefore, the depletion of MDSCs would strengthen immunity of tumor-bearing mice.

 

Recently, Prof. Yong Taik LIM’s group of Sungkyunkwan University reported a novel implantable, engineered 3-dimensional porous scaffolds which were designed to generate synergistic action between MDSC-depleting agents and cancer vaccines consisting of whole tumor lysates and nanogel-based adjuvants. The local peritumoral implantation of the synthetic immune niche (termed immuneCare-DISC, iCD) as a post-surgical treatment in an advanced-stage primary 4T1 breast tumor model generated systemic anti-tumor immunity and prevented tumor recurrence at the surgical site as well as the migration of residual tumor cells into the lungs, resulting in 100% survival.

 

These therapeutic outcomes were achieved through the inhibition of immunosuppressive MDSCs in tumors and spleens by releasing gemcitabine and recruitment/activation of dendritic cells, enhanced population of CD4+ and CD8+ T cells, and increased IFN-γ production by cancer vaccines from the iCD. This combined spatiotemporal modulation of tumor-derived immunosuppression and vaccine-induced immune stimulation through the iCD is expected to provide an immune niche for preventing of postoperative tumor recurrence and metastasis.

 

          Figure 1. Schematic diagram showing the design of the immuneCare-DISC

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