In Situ Modulation of Dendritic Cells by Injectable Thermosensitive Hydrogels for Cancer Vaccines in Mice

• Published in: Biomacromolecules Vol. 15; no. 10; pp. 3836 - 3845
• Main Authors: Liu, Yarong, Xiao, Liang, Joo, Kye-Il, Hu, Biliang, Fang, Jinxu, Wang, Pin
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 13.10.2014
• Subjects: Adjuvants, Immunologic - administration & dosage; Animals; Antigens, Neoplasm - immunology; Antineoplastic agents; Applied sciences; Biological and medical sciences; Cancer Vaccines - administration & dosage; Cancer Vaccines - immunology; Dendritic Cells - drug effects; Dendritic Cells - immunology; Exact sciences and technology; Female; Granulocyte-Macrophage Colony-Stimulating Factor - immunology; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Hydrogels - administration & dosage; Immunotherapy; Medical sciences; Mice; Mice, Inbred C57BL; Neoplasms - immunology; Neoplasms - metabolism; Organic polymers; Pharmacology. Drug treatments; Physicochemistry of polymers; Polyesters - administration & dosage; Polyethylene Glycols - administration & dosage; Properties and characterization; Solution and gel properties; Terpolymer; Injectable form; Lactic acid copolymer; Recruitment; Malignant melanoma; Release; Glycolic acid copolymer; Dendritic cell; Freeze drying; Immune response; Control release polymer; Rodentia; Physical gel; Vaccine; Malignant tumor; Ethylene oxide copolymer; Experimental study; In vitro; Biological activity; In vivo; Vertebrata; Mammalia; Mouse; Immunological adjuvant; Animal; Preparation; Diblock copolymer; Kinetics; Hydrogel; Ring opening copolymerization; Granulocyte macrophage colony stimulating factor; Cell migration; Cancer; Macrophage
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm501166j

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.