Abstract 3270: Modulating the tumor microenvironment and boosting T cell immunity with smart enzyme-loaded virus-like particles

Abstract Virus-like particles (VLPs) are biomaterials engineered to structurally and functionally mimic viruses without carrying viral genetic material, making them non-infectious. These icosahedral structures, composed of coat proteins, offer a versatile platform for chemical and genetic modifications. In this project, we modify VLPs with receptors targeting the overexpressed Platelet-Derived Growth Factor Receptor Beta (PDGFRβ) in cancers such as lung, liver, and colorectal cancers, enabling precise tumor targeting. Additionally, we address the metabolic challenges posed by the Warburg effect, which leads to lactate accumulation, acidifying the tumor microenvironment and impairing T cell function. To counteract this, we encapsulate lactate oxidase (LOX) and catalase (CAT) within VLPs. LOX reduces lactate levels by converting it to pyruvate and hydrogen peroxide (H2O2), while CAT mitigates excess H2O2, alleviating oxidative stress and hypoxia. Together, these enzymes reprogram the tumor microenvironment, enhance anti-tumor immunity, and suppress tumor progression. This innovative strategy combines targeted tumor delivery and immune activation, positioning enzyme-loaded VLPs as a promising platform for next-generation cancer therapies. Citation Format: Orikeda Trashi, Jeremiah Gassensmith. Modulating the tumor microenvironment and boosting T cell immunity with smart enzyme-loaded virus-like particles. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3270.