Improved nano-sized cell particles discovered to enhance cancer immunotherapy and reduce side effects
Electron micrograph of artificial extracellular vesicles (magnification 23,000x). Courtesy: NUS Yong Loo Lin School of Medicine
Immunotherapy is a type of cancer treatment that uses the body’s own immune system to fight cancer. It stimulates an immune response to more effectively recognize and attack cancer cells. Treatments may involve using substances to boost the immune system, teaching immune cells to target cancer, or using genetically engineered cells to target and kill cancer cells.
Immunotherapy is an important approach to cancer treatment, but its effectiveness is limited by the risk of immune-related side effects, as the immune system targets cancer cells but can also attack normal, healthy tissues. These side effects include inflammation and damage to various organs and tissues, leading to a range of symptoms and health complications.
A team led by Assistant Professor Ming Le from the Institute of Digital Medicine (WisDM) and Department of Pharmacology at the National University of Singapore’s Yong Loo Lin School of Medicine (NUS Medicine) has presented a novel delivery platform that significantly enhances the efficacy of cancer immunotherapy while reducing its associated side effects. This innovative approach, which leverages nano-sized particles called “extracellular vesicles” (EVs) released by cells, represents a major advancement in the field of cancer immunotherapy.
In this study, the researchers developed a technique to engineer EVs to carry multiple immune-boosting molecules, called “immunomodulatory ligands,” for the treatment of in vivo models of metastatic pancreatic cancer and malignant melanoma. This approach enhanced the therapeutic efficacy of ligands, specifically tumor necrosis factor receptor superfamily (TNFRSF) agonists, a subset of which are key in controlling the immune response to cancer.
The research team also discovered that this administration method enhances retention of the immune-enhancing ligand within the tumor, allowing for better therapeutic effects with smaller drug doses, thereby reducing the risk of side effects common to current immunotherapies.
The study, published in Molecular Therapy, demonstrates that a novel EV-based delivery approach can alter the immune composition of tumors, improving outcomes for cancer patients.
Immune cell composition in metastatic melanoma-affected lungs following treatment with immunomodulatory ligand alone (current standard of care) or EV-based immunomodulatory ligand delivery. EV-based delivery significantly altered the immune cell composition, increasing the proportion of key anti-tumor immune cells such as cytotoxic T cells (red) and helper T cells (blue), while simultaneously decreasing the frequency of tumor cells (black). Credit: NUS Yong Loo Lin School of Medicine
Tumor burden in the lungs of advanced metastatic melanoma. The main tumor nodule is indicated by the arrow. Courtesy of NUS Yong Loo Lin School of Medicine.
Notably, this approach has proven to consistently show superior results in terms of tumor-specific immune activation, suppression of tumor burden, overall survival, and resistance to tumor rechallenge (or recurrence) compared to the current clinical standard of care in which the ligand is administered in a free soluble form without the use of an EV-based delivery platform. This is noteworthy as it indicates that an EV-based delivery approach can enhance the treatment of existing tumors and prevent the recurrence of the same cancer in the future through the development of tumor-specific immune memory.
Assistant Professor Minh Le said, “We are pleased to present this novel EV-based delivery system that not only enhances the therapeutic efficacy of immune-modulating ligands but also significantly reduces systemic toxicity. Our findings pave the way for safer and more effective cancer immunotherapy, which may revolutionize the landscape of cancer treatment.”
“This new delivery platform has great potential to improve both the efficacy and safety of current immunotherapies, which often have limited efficacy and significant side effects. It may also enable the development of advanced therapies that more precisely target cancer cells while protecting healthy tissue,” added the study’s first author, Dr Migala Jayasinghe, from WisDM and the Department of Pharmacology at NUS Medical School.
The results of this research have been patented and the research group is currently working on advancing this technology to further enhance the broader application of immunotherapeutic ligand-based therapeutics. In parallel with plans to establish a clinical-stage startup, the technology developed through this research will be commercialized to make it accessible to other researchers in this and related fields.
Further information: Migara Kavishka Jayasinghe et al. “Extracellular vesicle surface display enhances therapeutic efficacy and safety profile of cancer immunotherapy.” Molecular Therapy (2024). DOI: 10.1016/j.ymthe.2024.07.013
Provided by National University of Singapore
Citation: Engineered nano-sized cell particles discovered to boost cancer immunotherapy and reduce side effects (September 16, 2024) Retrieved September 17, 2024 from https://phys.org/news/2024-09-nano-sized-cell-particles-boost.html
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