Uppsala University researchers have made a groundbreaking discovery in the field of CAR-T cell therapy, revealing that chimeric antigen receptor (CAR) molecules can transfer between immune cells through a process known as trogocytosis. This finding, published in Science Immunology, could have significant implications for improving cancer immunotherapy treatments.
Mechanism of CAR Molecule Transfer
The research team identified that CAR molecules, which are crucial components on the surface of engineered CAR-T cells used in cancer therapy, can be transferred to other T cells present in the tumor microenvironment. This transfer occurs through trogocytosis, a natural process where immune cells exchange surface molecules.
Dr. Stefano Barbera, the study's lead author and postdoctoral researcher at the Department of Immunology, Genetics and Pathology, explains: "Our study demonstrates that although cell–cell contact is needed, a specific molecule does not need a corresponding receptor on another cell to be trogocytosed. Instead, it is the membrane region surrounding the cell surface molecule that determines whether it can be transferred or not."
Challenging Previous Understanding
This discovery challenges the long-held hypothesis about how trogocytosis is regulated. Dr. Anna Dimberg, a senior author of the study, notes: "The fact that CAR molecules do not have a binding partner on other T cells further disproves the old hypothesis on how trogocytosis is regulated. We are very excited to be able to contribute with new biological insights to this process."
Implications for Cancer Treatment
While the exact biological role of CAR trogocytosis during CAR-T cell therapy remains under investigation, this new understanding opens up possibilities for therapeutic optimization. Dr. Magnus Essand, another senior author, highlights the potential clinical applications: "Now when we know how to regulate trogocytosis, we can design CAR molecules with and without the capacity to trogocytose and evaluate the different CAR molecules in advanced model systems and hopefully at a later stage in a clinical trial."
Future Research Directions
The research team is now focused on determining whether modulating trogocytosis - either increasing or reducing it - could enhance treatment efficacy or reduce side effects in CAR-T cell therapy. This work represents a significant step forward in understanding the complex interactions between engineered immune cells and their environment in cancer treatment.
