Targeting Dendritic Cells with Antigen-Containing Liposomes

Broekhoven, Christina L. van; Parish, Christopher R.; Demangel, Caroline; Britton, Warwick J.; Altin, Joseph G.

doi:10.1158/0008-5472.can-04-0138

Cited by 239 publications

(78 citation statements)

References 44 publications

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“…High-level expression of CD11c by DC renders it an attractive antigen target for vaccination purposes. Indeed, a previous study reported modifying liposomes with Fab fragments of the anti-CD11c antibody to specifically target DC [22], while others have shown enhancement of antibody responses [23] by targeting DC through CD11c. Castro et al [19] demonstrate that CD11c-targeting is also capable of facilitating strong CTL generation.…”

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confidence: 99%

CD11c: Not merely a murine DC marker, but also a useful vaccination target

Kurts

2008

Eur J Immunol

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The induction of robust CD4 + and CD8 + T cell responses is a central aim in antiviral and anticancer vaccination. To this end, dendritic cells (DC) need to capture the vaccine, process and present it on MHC class I and II molecules. The mechanisms by which DC acquire antigen predetermine the quantity and quality of the ensuing T cell activation. In this issue of the European Journal of Immunology, it is demonstrated that targeting antigen towards CD11c, an integrin expressed preferentially by murine DC, facilitates efficient CD4 + and CD8 + T cell activation. The underlying mechanisms involve efficient antigen delivery into the marginal zone and T/DC zone of the spleen. This commentary discusses these findings in the context of current knowledge on antigen presentation.

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confidence: 99%

CD11c: Not merely a murine DC marker, but also a useful vaccination target

Kurts

2008

Eur J Immunol

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“…This is a complicated and expensive process. 529 However, several recent studies used antibodies, antibody fragments, or other ligands that bind to dendritic cells to specifically deliver antigens in vivo. 529–534 Accordingly, peptides can be used to specifically target antigens in vivo.…”

Section: Use Of Peptides For Therapymentioning

confidence: 99%

Combinatorial Peptide Libraries: Mining for Cell-Binding Peptides

2013

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“…DEC-205 was also exploited as an internalization receptor for bispecific mAbs [111], the second paratope of which was against biotin, allowing the authors to couple biotinylated OVA as a model antigen. van Broekhoven et al [112] coupled an anti-DEC-205 mAb to the surface of plasma membrane vesicles prepared from the B16-OVA mouse melanoma or the surface of OVA-containing liposomes. Both these preparations targeted DCs and stimulated anti-OVA CTL responses and tumor protection in immunized mice.…”

Section: Targeting Antigens To DC Surface Receptorsmentioning

confidence: 99%

Targeting Tumor-Associated Antigens to the MHC Class I Presentation Pathway

Gross

Margalit²

2007

EMIDDT

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There is little doubt that cytotoxic T lymphocytes (CTLs) can kill tumor cells in-vivo. However, most CTL-inducing immunization protocols examined so far in cancer patients have yielded only limited clinical benefits, underscoring the urge to improve current approaches for the effective induction of tumor-reactive CTLs. The tumor side of the immunological frontline is armed with large masses, high mutability and an arsenal of immune evasion and suppression mechanisms. Accordingly, the confronting CTLs should come in large numbers, recognize an assortment of MHC class I (MHC-I) bound tumor-associated peptides and be brought into action under effective immunostimulatory conditions. Naïve CTLs are activated to become effector cells in secondary lymphoid organs, following their productive encounter with MHC-I-bound peptides at the surface of dendritic cells (DCs). Therefore, many cancer vaccines under development focus on the optimization of peptide presentation by DCs at this critical stage. The elucidation of discrete steps and the subsequent identification of inherent bottlenecks in the MHC-I antigen presentation pathway have fueled elaborate efforts to enhance vaccine efficacy by the rational targeting of proteins or peptides, formulated into these vaccines, to this pathway. Protein- and gene-based strategies are accordingly devised to deliver tumor-associated peptides to selected cellular compartments, which are essential for the generation of functional CTL ligands. Many of these strategies target the conventional, endogenous route, while others harness the unique pathways that enable DCs to present exogenous antigens, known as cross-presentation. Here we dissect the intricate machinery that produces CTL ligands and examine how knowledge-based cancer vaccines can target the sequence of workstations, biochemical utensils and molecular intermediates comprising this production line.

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Targeting Dendritic Cells with Antigen-Containing Liposomes

Abstract: ABSTRACT

Cited by 239 publications

References 44 publications

CD11c: Not merely a murine DC marker, but also a useful vaccination target

CD11c: Not merely a murine DC marker, but also a useful vaccination target

Combinatorial Peptide Libraries: Mining for Cell-Binding Peptides

Targeting Tumor-Associated Antigens to the MHC Class I Presentation Pathway

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