Publications & Reports

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

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


Non-antigen-specific stimulatory cancer immunotherapies are commonly complicated by off-target effects. Antigen-specific immunotherapy, combining viral tumor antigen or personalised neo-epitopes 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-CLEC-9A mAb conjugates target cross-presenting DCs, adjuvant must be co-delivered for cytotoxic T-cell (CTL) induction. We functionalized tailored nanoemulsions encapsulating tumor antigens to target Clec9A (Clec9A-TNE). Clec9A-TNE encapsulating ovalbumin (OVA) antigen targeted and activated cross-presenting DCs without additional adjuvant, promoting antigen-specific CD4+ and CD8+ T cell proliferation, CTL and antibody responses. OVA-Clec9A-TNE-induced DC activation required CD4 and CD8 epitopes, CD40 and IFN-alpha. Clec9A-TNE encapsulating human papillomavirus (HPV) E6-E7 significantly suppressed HPV-associated tumor growth while E6-E7-CpG did not. Clec9A-TNE loaded with pooled B16F10 melanoma neo-epitopes induced epitope-specific CD4+ and CD8+ T cell responses, permitting selection of immunogenic neo-epitopes. Clec9A-TNE encapsulating six neo-epitopes significantly suppressed B16-F10 melanoma growth in a CD4 T cell-dependent manner. Thus, cross-presenting DCs targeted with antigen-Clec9A-TNE stimulate therapeutically-effective tumor-specific immunity, dependent on T cell help.

Link to publisher’s web site


  • Journal: The Journal of Clinical Investigation
  • Published: 01/05/2018
  • Volume: 128
  • Issue: 5
  • Pagination: 1971-1984