Publications & Reports

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

Tullett KM, Leal Rojas IM, Minoda Y, Tan PS, Zhang JG, Smith C, Khanna R, Shortman K, Caminschi I, Lahoud MH, Radford KJ
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 Di

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.

Link to publisher’s web site

This project was supported by Prostate Cancer Foundation of Australia grant PG2110 and National Health and Medical Research Council of Australia grants 604306, 1008986, 1025201, 1078987, 1082665, and 1016647, and the Mater Foundation. K. Tullett is supported by a University of Queensland International PhD Scholarship. The Translational Research Institute is supported by the Australian Government. This work was also made possible through Victorian State Government Operational Infrastructure Support and Downloaded from http://insight.jci.org on October 6, 2016. http://dx.doi.org/10.1172/jci.insight.87102 insight.jci.org doi:10.1172/jci.insight.87102 1 1 Technical A dvance Australian Government NHMRC IRIISS grant number 9000220

Publication

  • Journal: JCI insight
  • Published: 19/05/2016
  • Volume: 1
  • Issue: 7
  • Pagination: e87102