Journal article

Self-adjuvanting nanoemulsion targeting dendritic cell receptor Clec9A enables antigen-specific immunotherapy

B Zeng, APJ Middelberg, A Gemiarto, K MacDonald, AG Baxter, M Talekar, D Moi, KM Tullett, I Caminschi, MH Lahoud, R Mazzieri, R Dolcetti, R Thomas

Journal of Clinical Investigation | AMER SOC CLINICAL INVESTIGATION INC | Published : 2018

Abstract

Non-antigen-specific stimulatory cancer immunotherapies are commonly complicated by off-target effects. Antigen-specific immunotherapy, combining viral tumor antigen or personalized neoepitopes with immune targeting, offers a solution. However, the lack of flexible systems targeting tumor antigens to cross-presenting dendritic cells (DCs) limits clinical development. Although antigen-anti-Clec9A mAb conjugates target cross-presenting DCs, adjuvant must be codelivered for cytotoxic T lymphocyte (CTL) induction. We functionalized tailored nanoemulsions encapsulating tumor antigens to target Clec9A (Clec9A-TNE). Clec9A-TNE encapsulating OVA antigen targeted and activated cross-presenting DCs wi..

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Grants

Awarded by National Health and Medical Research Council


Funding Acknowledgements

The work was supported by National Health and Medical Research Council (NHMRC) grants 1083192, 1082665, and 1083747, and by a grant from the Australian Skin and Skin Cancer Centre. RT was supported by Arthritis Queensland and an NHMRC Research Fellowship. ML and IC were supported by a Bill and Janina Amiet Fellowship. We thank Christian Engwerda (QIMR Berghofer) and Ian Frazer (Diamantina Institute, University of Queensland) for supplying mice and Hendrik Nel for technical assistance.