Unknown

Dataset Information

0

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


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 without additional adjuvant, promoting antigen-specific CD4+ and CD8+ T cell proliferation and CTL and antibody responses. OVA-Clec9A-TNE-induced DC activation required CD4 and CD8 epitopes, CD40, and IFN-?. Clec9A-TNE encapsulating HPV E6/E7 significantly suppressed HPV-associated tumor growth, while E6/E7-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-dependent manner. Thus, cross-presenting DCs targeted with antigen-Clec9A-TNE stimulate therapeutically effective tumor-specific immunity, dependent on T cell help.

SUBMITTER: Zeng B 

PROVIDER: S-EPMC5919883 | biostudies-other | 2018 May

REPOSITORIES: biostudies-other

Similar Datasets

| S-EPMC9179507 | biostudies-literature
| S-EPMC5825289 | biostudies-literature
| S-EPMC6151129 | biostudies-literature
| S-EPMC5708771 | biostudies-literature
| S-EPMC8407156 | biostudies-literature
| S-EPMC5958800 | biostudies-literature
| S-EPMC6124532 | biostudies-literature
| S-EPMC2575478 | biostudies-literature
| S-EPMC3766769 | biostudies-literature
| S-EPMC5130018 | biostudies-literature