1147 Bioengineered virus-like particles as novel immunotherapy: enhancing T cell recruitment in cancer treatment
Year: 2024
Type: conference-abstract
Abstract: Background Virus-like particles (VLPs) are biomaterials engineered to mimic viruses structurally and functionally while lacking viral genetic material, ensuring they are non-infectious. Comprising coat proteins assembled as pentamers and hexamers in an icosahedral shape, VLPs are versatile bio-tools adaptable through supramolecular chemistry and genetic modifications. Our objective is to tailor VLP exteriors with specific receptors targeting the overexpressed Platelet-Derived Growth Factor Receptor Beta gene found in various cancers, including lung, liver, and colorectal cancers. This modification aims to enhance VLPs’ ability to selectively target tumor cells that overexpress this receptor, potentially improving the efficacy and specificity of cancer therapies. Tumor cells go through a metabolic effect Warburg effect, increasing glucose uptake and generating lactate, which acidifies the tumor microenvironment, promoting tumor progression and invasion. Lactate also induces a metabolic shift in T cells towards glycolysis, impairing their function, cytokine production, and cytotoxic effects on cancer cells. Moreover, lactate suppresses pro-inflammatory cytokine secretion by T cells and enhances the immunosuppressive activity of regulatory T cells (Tregs), further hindering anti-tumor immunity. Lactate oxidase (LOX) is an enzyme that utilizes lactate and oxygen to produce pyruvate and hydrogen peroxide (H2O2). The production of H2O2 is crucial for reducing lactate levels in tumors, killing tumor cells, and modulating the tumor microenvironment. However, the hypoxic nature of tumors, due to high oxygen consumption by proliferating cells, limits LOX catalytic activity. Excessive H2O2 production can induce apoptosis and oxidative damage in normal cells. Catalase (CAT), another enzyme, catalyzes the breakdown of H2O2 into oxygen and water. This project aims to encapsulate LOX and CAT inside VLPs, creating a dual enzyme platform. These modified VLPs will be used for targeted therapy, delivering them intravenously to suppress tumor growth and modulate immune system activation. Methods This study uses a dual-plasmid system to create VLPs with internal LOX-CAT enzymes and external receptors. After purification, these engineered VLPs will be tested in vitro on PDGFR Beta-overexpressing cells and in vivo for targeting and tumor-killing efficacy. Flow cytometry will assess immune cell activation, aiming to validate these modified VLPs for targeted cancer therapy. Results We have shown in-vivo that we can target different types of tumors overexpressing PDGFR B. We have also shown that we can cause a cytotoxic effect and immune cells activation. Conclusions In summary we aim to show to show in-vivo VLPs’ targeting capabilities to enhance therapeutic efficacy while minimizing off-target effects, offering a promising immunotherapy treatment.
Authors: Orikeda Trashi, Orikeda
Institution: The University of Texas at Dallas
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W4404065302