Study Paves the Way for More Effective Cancer Treatments – Led by Associate Professor Triantafyllos Stylianopoulos

An international research collaboration between the University of Cyprus’ School of Engineering, Massachusetts General Hospital, and Harvard Medical School sheds new light on improving the effectiveness of CAR-T cell therapies in solid tumors.

The study, published in the prestigious journal PNAS (Proceedings of the National Academy of Sciences), proposes new strategies to enhance CAR-T cell penetration and activity through the normalization of tumor vasculature and the tumor microenvironment. Titled “Physiologically-based pharmacokinetic model for CAR-T cell delivery and efficacy in solid tumors”, the research was conducted under the guidance of Dr. Triantafyllos Stylianopoulos (Cancer Biophysics Laboratory, University of Cyprus) and Dr. Rakesh K. Jain (Massachusetts General Hospital/Harvard), with first author Dr. Andreas Chatzigeorgiou and participation from Dr. Lance L. Munn.

CAR-T cell therapy, an innovative form of immunotherapy in which a patient’s T lymphocytes are reprogrammed to attack cancer cells, has already revolutionized treatment for hematological malignancies. However, its application in solid tumors, such as glioblastoma or pancreatic cancer, remains challenging due to physical barriers in the tumor microenvironment.

The researchers investigated how interventions targeting vascular structure (via anti-VEGF agents) or reducing collagen and hyaluronic acid levels could enhance CAR-T cell infiltration and efficacy.

The team developed an advanced computational model simulating the movement and effectiveness of CAR-T cells in the human body, incorporating preclinical data. For the first time, the model combines parameters such as immune response, vascular structure, and tumor stroma, allowing simulations of various therapeutic scenarios, including different doses and timing, as well as combinations with vascular or stromal normalization.

This approach serves as an important tool for designing future experimental and clinical applications, providing a new framework for understanding the interactions between immunotherapy and the tumor microenvironment.

According to the results, improving vascular structure can increase CAR-T cell efficacy by up to 50%, while enabling a reduction in the required dose by nearly fivefold. Combination therapies targeting both tumor vasculature and stroma proved most effective, offering hope for safer and more personalized treatments.

The research team at the University of Cyprus’ School of Engineering now plans experimental validation of the findings and the development of a new computational tool that will utilize patient data to personalize therapies.

By combining computational modeling, biological data, and clinical expertise, this approach is expected to pave the way for more targeted, effective, and accessible cancer treatments.

As Dr. Stylianopoulos emphasizes, “Mathematical modeling is becoming a powerful tool for improving anti-cancer therapy and translating research from the laboratory to the patient.”