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In situ modulation of dendritic cells by injectable thermosensitive hydrogels for cancer vaccines in mice.

Liu Y, Xiao L, Joo KI, Hu B, Fang J, Wang P - Biomacromolecules (2014)

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

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.

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.

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Related in: MedlinePlus

Schematic Illustration of the Two-StepHybrid Strategy for a CancerVaccineStep 1: Sustainable releaseof GM-CSF from the injectable thermosensitive mPEG–PLGA hydrogelsrecruits host dendritic cells (DCs) to the site of administration.Step 2: Viral or nonviral vectors carrying immunogens can be deliveredin situ to the resident DCs in hydrogels to enhance antigen uptakeefficiency, thereby improving anticancer immunity.
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sch1: Schematic Illustration of the Two-StepHybrid Strategy for a CancerVaccineStep 1: Sustainable releaseof GM-CSF from the injectable thermosensitive mPEG–PLGA hydrogelsrecruits host dendritic cells (DCs) to the site of administration.Step 2: Viral or nonviral vectors carrying immunogens can be deliveredin situ to the resident DCs in hydrogels to enhance antigen uptakeefficiency, thereby improving anticancer immunity.


In situ modulation of dendritic cells by injectable thermosensitive hydrogels for cancer vaccines in mice.

Liu Y, Xiao L, Joo KI, Hu B, Fang J, Wang P - Biomacromolecules (2014)

Schematic Illustration of the Two-StepHybrid Strategy for a CancerVaccineStep 1: Sustainable releaseof GM-CSF from the injectable thermosensitive mPEG–PLGA hydrogelsrecruits host dendritic cells (DCs) to the site of administration.Step 2: Viral or nonviral vectors carrying immunogens can be deliveredin situ to the resident DCs in hydrogels to enhance antigen uptakeefficiency, thereby improving anticancer immunity.
© Copyright Policy - editor-choice
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4195289&req=5

sch1: Schematic Illustration of the Two-StepHybrid Strategy for a CancerVaccineStep 1: Sustainable releaseof GM-CSF from the injectable thermosensitive mPEG–PLGA hydrogelsrecruits host dendritic cells (DCs) to the site of administration.Step 2: Viral or nonviral vectors carrying immunogens can be deliveredin situ to the resident DCs in hydrogels to enhance antigen uptakeefficiency, thereby improving anticancer immunity.
Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus