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Glycan-modified liposomes boost CD4+ and CD8+ T-cell responses by targeting DC-SIGN on dendritic cells
- Source :
-
Journal of Controlled Release . May2012, Vol. 160 Issue 1, p88-95. 8p. - Publication Year :
- 2012
-
Abstract
- Abstract: Cancer immunotherapy requires potent tumor-specific CD8+ and CD4+ T-cell responses, initiated by dendritic cells (DCs). Tumor antigens can be specifically targeted to DCs in vivo by exploiting their expression of C-type lectin receptors (CLR), which bind carbohydrate structures on antigens, resulting in internalization and antigen presentation to T-cells. We explored the potential of glycan-modified liposomes to target antigens to DCs to boost murine and human T-cell responses. Since DC-SIGN is a CLR expressed on DCs, liposomes were modified with DC-SIGN-binding glycans Lewis (Le)B or LeX. Glycan modification of liposomes resulted in increased binding and internalization by BMDCs expressing human DC-SIGN. In the presence of LPS, this led to 100-fold more efficient presentation of the encapsulated antigens to CD4+ and CD8+ T-cells compared to unmodified liposomes or soluble antigen. Similarly, incubation of human moDC with melanoma antigen MART-1-encapsulated liposomes coated with LeX in the presence of LPS led to enhanced antigen-presentation to MART-1-specific CD8+ T-cell clones. Moreover, this formulation drove primary CD8+ T-cells to differentiate into high numbers of tetramer-specific, IFN-γ-producing effector T-cells. Together, our data demonstrate the potency of a glycoliposome-based vaccine targeting DC-SIGN for CD4+ and CD8+ effector T-cell activation. This approach may offer improved options for treatment of cancer patients and opens the way to in situ DC-targeted vaccination. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 01683659
- Volume :
- 160
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Controlled Release
- Publication Type :
- Academic Journal
- Accession number :
- 76157805
- Full Text :
- https://doi.org/10.1016/j.jconrel.2012.02.007