title: In situ modulation of dendritic cells by injectable thermosensitive hydrogels for cancer vaccines in mice.
abstract: Attempts to develop cell-based cancer vaccines have shown limited efficacy, partly because transplanted dendritic cells (DCs) do not survive long enough to reach the lymph nodes. The development of biomaterials capable of modulating DCs in situ to enhance antigen uptake and presentation has emerged as a novel method toward developing more efficient 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 thermosensitive mPEG-PLGA hydrogel through sustained release of chemoattractants, in particular, granulocyte-macrophage colony-stimulating factor (GM-CSF). Then, these resident DCs can be loaded with cancer antigens through the use of viral or nonviral vectors. We demonstrate that GM-CSF-releasing mPEG-PLGA hydrogels successfully recruit and house DCs and macrophages, allowing the subsequent introduction of antigens by vectors to activate the resident cells, thus, initiating antigen presentation and triggering immune response. Moreover, this two-step hybrid strategy generates a high level of tumor-specific immunity, as demonstrated in both prophylactic and therapeutic models of murine melanoma. This injectable thermosensitive hydrogel shows great promise as an adjuvant for cancer vaccines, potentially providing a new approach for cell therapies through in situ modulation of cells.
authors.affiliation: Mork Family Department of Chemical Engineering and Materials Science, ‡Department of Biomedical Engineering, and §Department of Pharmacology and Pharmaceutical Sciences, University of Southern California , Los Angeles, California 90089, United States.
authors.forename: Yarong
authors.initials: Y
authors.lastname: Liu
authors.forename: Liang
authors.initials: L
authors.lastname: Xiao
authors.forename: Kye-Il
authors.initials: KI
authors.lastname: Joo
authors.forename: Biliang
authors.initials: B
authors.lastname: Hu
authors.forename: Jinxu
authors.initials: J
authors.lastname: Fang
authors.forename: Pin
authors.initials: P
authors.lastname: Wang
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism; D020100:Hydrogels / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism; D011091:Polyesters / Q000008:administration & dosage; D011092:Polyethylene Glycols / Q000008:administration & dosage
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D020100:Hydrogels; D011091:Polyesters; C558447:methoxypolyethyleneglycol-poly(lactic-co-glycolic acid); D011092:Polyethylene Glycols; D016178:Granulocyte-Macrophage Colony-Stimulating Factor