Nano-sized engineered cell particles improve cancer immunotherapy and reduce side effects

Immunotherapy is a type of cancer treatment that uses the body’s immune system to fight cancer. This involves boosting the immune response to recognize and attack cancer cells more effectively. Treatment involves using substances that boost the immune system, teaching immune cells to target cancer, or using modified cells to specifically target and kill cancer cells.

Although it is a key approach in cancer treatment, the effectiveness of immunotherapy is limited by the risk of immune-related side effects, as the immune system, while targeting cancer cells, can also attack normal, healthy tissues. These side effects include inflammation or damage to various organs and tissues, causing a range of symptoms or health complications.

A team led by Assistant Professor Minh Le from the Institute of Digital Medicine (WisDM) and the Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine) has unveiled a novel delivery platform that significantly improves the efficacy of cancer immunotherapy while reducing associated side effects. This innovative approach, which relies on nano-sized particles released by cells, called extracellular vesicles (EVs), represents a major advancement in the field of cancer immunotherapy.

In this study, the researchers developed a technique to modify EVs to carry several immune-stimulating molecules, called “immunomodulatory ligands,” for the treatment of in vivo models of metastatic pancreatic cancer and melanoma. This approach improved the therapeutic efficacy of the ligands, particularly tumor necrosis factor receptor subfamily (TNFRSF) agonists, which play a critical role in controlling immune responses against cancer.

The team also found that the delivery method improved the retention of immune-stimulating ligands in the tumor, allowing for better therapeutic effects with lower drug doses, which in turn reduced the risk of side effects often seen in current immunotherapy treatments.

Published in Molecular therapyThe study demonstrates that the novel EV-based delivery approach can alter tumor immune composition to improve treatment outcomes for cancer patients.

Of note, this approach has been consistently shown to be more effective in terms of tumor-specific immune activation, tumor burden suppression, overall survival, and resistance to tumor re-exposure (or recurrence), compared to the current clinical standard of care, where ligands are administered in their free soluble form without the EV-based delivery platform. This is remarkable as it indicates that the EV-based delivery approach is capable of improving the treatment of existing tumors and preventing the recurrence of the same cancer in the future via the development of tumor-specific immune memory.

Assistant Professor Minh Le said: “We are delighted to present this novel EV-based delivery system that not only improves the therapeutic efficacy of immunomodulatory ligands but also significantly reduces systemic toxicity. Our results pave the way for safer and more effective cancer immunotherapies, potentially transforming the landscape of cancer treatment.”

The study’s first author, Dr Migara Jayasinghe from WisDM and the Department of Pharmacology at NUS Medicine, added: “This new delivery platform holds great potential to improve both the efficacy and safety of current immunotherapies, which often have limited results and major side effects. It also enables the development of advanced treatments that can more precisely target cancer cells while protecting healthy tissues.”

The results of this study have been patented and the research group is now working to advance this technology to further improve the broader application of ligand-based immunotherapeutics. In parallel with plans to create a clinical-stage start-up, the technologies developed in this study will be commercialized to facilitate access to other researchers in the field and in related disciplines.