1. Intradermal vaccination with a phytoglycogen nanoparticle and STING agonist induces cytotoxic T lymphocyte-mediated antitumor immunity
- Author
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Juan F. Hernandez-Franco, Imran M. Jan, Bennett D. Elzey, and Harm HogenEsch
- Subjects
Immunologic diseases. Allergy ,RC581-607 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract A critical aspect of cancer vaccine development is the formulation with effective adjuvants. This study evaluated whether combining a cationic plant-derived nanoparticle adjuvant (Nano-11) with the clinically tested STING agonist ADU-S100 (MIW815) could stimulate anticancer immunity by intradermal vaccination. Nano-11 combined with ADU-S100 (NanoST) synergistically activated antigen-presenting cells, facilitating protein antigen cross-presentation in vitro and in vivo. Intradermal vaccination using ovalbumin (OVA) as a tumor antigen and combined with Nano-11 or NanoST prevented the development of murine B16-OVA melanoma and E.G7-OVA lymphoma tumors. The antitumor immunity was abolished by CD8+ T cell depletion but not by CD4+ T cell depletion. Therapeutic vaccination with NanoST increased mouse survival by inhibiting B16-OVA tumor growth, and this effect was further enhanced by PD-1 checkpoint blockade. Our study provides a strong rationale for developing NanoST as an adjuvant for intradermal vaccination and next-generation preventative and therapeutic cancer vaccines by STING-targeted activation.
- Published
- 2024
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