%0 Journal Article
%T Self-adjuvanting nanoemulsion targeting dendritic cell receptor Clec9A enables antigen-specific immunotherapy
%A Adrian Gemiarto
%A Alan G. Baxter
%A Anton P.J. Middelberg
%A Bijun Zeng
%A Davide Moi
%A Irina Caminschi
%A Kelli MacDonald
%A Kirsteen M. Tullett
%A Meghna Talekar
%A Mireille H. Lahoud
%A Ranjeny Thomas
%A Riccardo Dolcetti
%A Roberta Mazzieri
%J The Journal of Clinical Investigation
%D 2018
%R 10.1172/JCI96791
%X Non每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每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 without additional adjuvant, promoting antigen-specific CD4+ and CD8+ T cell proliferation and CTL and antibody responses. OVA-Clec9A-TNE每induced DC activation required CD4 and CD8 epitopes, CD40, and IFN-汐. Clec9A-TNE encapsulating HPV E6/E7 significantly suppressed HPV-associated tumor growth, while E6/E7每CpG did not. Clec9A-TNE loaded with pooled B16-F10 melanoma neoepitopes induced epitope-specific CD4+ and CD8+ T cell responses, permitting selection of immunogenic neoepitopes. Clec9A-TNE encapsulating 6 neoepitopes significantly suppressed B16-F10 melanoma growth in a CD4+ T cell每dependent manner. Thus, cross-presenting DCs targeted with antigen每Clec9A-TNE stimulate therapeutically effective tumor-specific immunity, dependent on T cell help
%U https://www.jci.org/articles/view/96791