(690d) Injectable Thermo-Sensitive Hydrogel As an Adjuvant: In Situ Modulation of Dendritic Cells for Cancer Vaccine

Authors: 
Liu, Y., University of Southern California
Joo, K. I., University of Southern California
Xiao, L., University of Southern California
Wang, P., University of Southern California

Attempts to develop cell-based cancer vaccines have shown limited efficacy due to the failure of transplanted dendritic cells (DCs) to survive long enough to reach the lymph nodes. The development of materials that can modulate DCs in situ to enhance antigen uptake and presentation has emerged as a novel method toward developing high quality cancer vaccines. Here, we propose a two-step hybrid strategy to produce a more robust cell-based cancer vaccine in situ.  First, a significant number of DCs are recruited to an injectable thermo-sensitive mPEG-PLGA hydrogel through sustained release of chemo-attractants, like granulocyte-macrophage colony-stimulating factor (GM-CSF).  Then, these resident DCs can be loaded with cancer antigens through the use of viral or non-viral vectors. We demonstrate that GM-CSF releasing mPEG-PLGA hydrogels successfully recruit and house DCs and macrophages, allowing subsequent introduction of antigens by vectors to activate the resident cells, thus initiating antigen presentation and boosting immune response. Moreover, this two-step hybrid strategy generates a high level of specific anti-tumor immunity demonstrated in both prophylactic and therapeutic models of melanoma. This injectable thermo-sensitive hydrogel shows great promise as an adjuvant for cancer vaccines, potentially providing a new approach for cell therapies through in situ modulation of cells.
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