An international research collaboration between the University of Cyprus, Massachusetts General Hospital and Harvard Medical School sheds new light on improving the effectiveness of CAR-T cell therapies in solid tumors.
According to an announcement by the University of Cyprus, the study, published in the prestigious scientific journal PNAS (Proceedings of the National Academy of Sciences), proposes new strategies to enhance the penetration and action of CAR-T cells through the normalization of vessels and the tumor microenvironment.
The study, entitled "Physiologically-based pharmacokinetic model for CAR-T cell delivery and efficacy in solid tumors", was carried out under the guidance of Drs. Rakesh K. Jain (Massachusetts General Hospital/Harvard) and Drs. Triantafyllos Stylianopoulos (University of Cyprus), with first author Dr. Andreas Hatzigeorgiou and the participation of Dr. Lance L. Munn.
CAR-T cell therapy – a pioneering form of immunotherapy where a patient's T-lymphocytes are reprogrammed to destroy cancer cells – has already revolutionized hematological malignancies.
However, its application in solid tumors such as glioblastoma or pancreatic cancer remains challenging due to the physical barriers in the tumor microenvironment.
The researchers investigated how interventions aimed at improving vascular structure (via anti-VEGF agents) or reducing collagen and hyaluronic acid levels can enhance the penetration and action of CAR-T cells.
The team developed an advanced computational model that simulates the movement and effectiveness of CAR-T cells in the human body, incorporating data from preclinical studies. The model combines for the first time parameters such as immune response, vascular structure and tumor stroma, allowing the simulation of various therapeutic scenarios – from different doses and times of administration, to combinations with vascular or stromal normalization.
This approach is an important tool for planning future experimental and clinical applications, offering a new framework for understanding the interactions between immunotherapy and the tumor microenvironment.
According to the results, improving the vascular structure can increase the effectiveness of CAR-T cells by up to 50%, while allowing for a reduction of the required dose by almost five times. Combination therapies that target both the vasculature and the tumor stroma have proven to be the most effective, offering hope for safer and more personalized treatments.
The University of Cyprus research team is now planning experimental confirmation of the findings and the development of a new computational tool that will utilize patient data to personalize treatments.
The combination of computational modeling, biological data, and clinical experience is expected to pave the way for more targeted, effective, and affordable cancer treatments.
As pointed out by Dr. Stylianopoulos, "mathematical modeling is turning into a powerful tool for improving anticancer therapy and transferring research from the laboratory to the patient."
