In vivo targeting of (Neo)-antigens to CleC9A+ cross-presenting dendritic cells to improve personalised cancer immunotherapy

Despite the success of immune checkpoint inhibitors, a large number of cancer patients do not benefit from this therapy. Early research indicates that a therapeutic combination of cancer vaccines with checkpoint inhibitors may lead to synergistic effects and higher response rates than monotherapy. Nevertheless, cancer vaccines of high potency and antigen-specificity are not available yet due to the limited efficacy of current strategies to target antigen and adjuvants to cross-presenting dendritic cells (DCs). To overcome these limitations, we have developed a versatile antigen delivery platform based on the use of a self-adjuvanting tailored nanoemulsion (TNE) functionalized to target Clec9A, a DC-specific endocytic receptor expressed by cross-presenting DCs in mice and humans. Our findings indicate that our Clec9A-targeting vaccination platform can efficiently exploit the immunogenicity of the unique epitopes expressed by oncogenic viruses or generated by somatic mutations, which are the most potent antigens for cancer immunotherapy. This novel strategy may improve the feasibility and efficacy of personalized immunotherapy for cancer patients.