A STING-activating nanovaccine for cancer immunotherapy

Abstract

Generation of tumor-specific T cells is critically important for cancer immunotherapy1,2. A major challenge in achieving a robust T cell response is the spatio-temporal orchestration of antigen cross-presentation in antigen presenting cells (APCs) with innate stimulation. Here we report a minimalist nanovaccine by a simple physical mixture of an antigen with a synthetic polymeric nanoparticle, PC7A NP, which generated a strong cytotoxic T cell response with low systemic cytokine expression. Mechanistically, PC7A NP achieved efficient cytosolic delivery of tumor antigens to APCs in draining lymph nodes leading to increased surface presentation while simultaneously activating type I interferon-stimulated genes. This effect was dependent on STING but not Toll-like receptor or MAVS pathway. Nanovaccine produced potent tumor growth inhibition in melanoma, colon cancer, and human papilloma virus-E6/E7 tumor models. Combination of PC7A nanovaccine with an anti-PD-1 antibody showed great synergy with 100% survival over 60 days in a TC-1 tumor model. Rechallenging of these tumor-free animals with TC-1 cells led to complete inhibition of tumor growth, suggesting generation of long-term antitumor memory. The STING-activating nanovaccine offers a simple, safe and robust strategy in boosting anti-tumor immunity for cancer immunotherapy.

Photosensitizer Micelles Together with IDO Inhibitor Enhance Cancer Photothermal Therapy and Immunotherapy

“…The ongoing development of nanoparticles not only improves the targeting and bioavailability of drugs and develops new therapeutic methods, such as photothermal therapy and nanovaccines, but also provides a suitable carrier for the realization of combination therapy 2, 3, 4, 5, 6, 7. Moreover, some nanoparticle‐based systems can strengthen the immune response in tumor immunotherapy, which has attracted much attention 8, 9, 10, 11…”

Improving Vaccine and Immunotherapy Design Using Biomaterials

“…For example, iPEMs built on microneedles using melanoma peptides and TLRas have been used for delivery to the immune-rich dermal layer in mice to generate melanoma-specific T cells [60]. In another approach, spontaneous micelle vaccines composed of tumor peptides and synthetic polymers that activate STING (stimulator of interferon gene) signaling generated strong antitumor inhibition in multiple mouse models [61]. In particular, these examples underscore the theme that carriers can be engineered to also actively trigger desirable immune pathways.…”

Deployment and exploitation of nanotechnology nanomaterials and nanomedicine

“…Recent examples are NP that enhance the function of antigen presenting cells leading to strong anti-tumour T cell cytotoxicity [112,113]. A number of biotechnology/pharmaceutical companies are pursuing NP-based vaccines [114].…”