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JCI Insight. 2016 May 19;1(7):e87102.

Targeting CLEC9A delivers antigen to human CD141+ DC for CD4+ and CD8+T cell recognition.

Author information

1
Mater Research Institute - University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.; University of Queensland, School of Medicine, Brisbane, Queensland, Australia.; Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria, Australia.; Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.
2
Mater Research Institute - University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
3
Mater Research Institute - University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.; University of Queensland, School of Biomedical Sciences, Brisbane, Queensland, Australia.
4
Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria, Australia.; Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.
5
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia.
6
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
7
Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria, Australia.; Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.; Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, Australia.

Abstract

DC-based vaccines that initiate T cell responses are well tolerated and have demonstrated efficacy for tumor immunotherapy, with the potential to be combined with other therapies. Targeting vaccine antigens (Ag) directly to the DCs in vivo is more effective than cell-based therapies in mouse models and is therefore a promising strategy to translate to humans. The human CD141+ DCs are considered the most clinically relevant for initiating CD8+ T cell responses critical for killing tumors or infected cells, and they specifically express the C-type lectin-like receptor CLEC9A that facilitates presentation of Ag by these DCs. We have therefore developed a human chimeric Ab that specifically targets CLEC9A on CD141+ DCs in vitro and in vivo. These human chimeric Abs are highly effective at delivering Ag to DCs for recognition by both CD4+ and CD8+ T cells. Given the importance of these cellular responses for antitumor or antiviral immunity, and the superior specificity of anti-CLEC9A Abs for this DC subset, this approach warrants further development for vaccines.

PMID:
27699265
PMCID:
PMC5033826
DOI:
10.1172/jci.insight.87102
[Indexed for MEDLINE]
Free PMC Article

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