Robust Anti‐Tumor T Cell Response with Efficient Intratumoral Infiltration by Nanodisc Cancer Immunotherapy

Abstract

Potent anti‐tumor T cell response and efficient intratumoral T cell infiltration are the major challenges for therapeutic cancer vaccines. To address these issues, a nanovaccine system is designed to promote anti‐tumor T cell responses, and intratumoral infiltration is examined in various murine tumor models. Subcutaneous vaccination with nanodiscs carrying human papillomavirus (HPV)‐16 E7 antigen elicits as high as ∼32% E7‐specific CD8α+ T cell responses in circulation, representing a 29‐fold improvement over the soluble peptide vaccination. Importantly, nanodisc vaccination also promotes robust intratumoral T cell infiltration and eliminates HPV16 E6/E7‐expressing TC‐1 tumors at mucosal sites, including lungs, inner lip, and intravaginal tissues. In a benchmark study with a live Listeria vaccine combined with anti‐PD‐1 IgG, nanodiscs plus anti‐PD‐1 immune checkpoint blockade elicits comparable levels of T cell responses with anti‐tumor efficacy. Furthermore, compared with Complete Freund’s Adjuvant combined with tetanus toxoid, nanodisc vaccination in HLA‐A02 mice generates >200‐fold stronger IFN‐γ+ T cell responses against a neoantigen from an HLA‐A02 melanoma patient. Overall, these results show that the nanodisc system is a promising cancer vaccine platform for inducing anti‐tumor T cell responses.Efficient infiltration of T cells in solid cancer is a major challenge for cancer immunotherapy. A nanoparticle vaccine system is developed to promote T cell infiltration into peripheral mucosal tissues and eliminate disseminated tumors. Nanodiscs are broadly applicable with a wide range of tumor antigens, thus providing a versatile and potent vaccine platform for eliciting T cell immunity.