Portuguese fine-tune "personalized cells" against cancer

They are called CAR T cells, and they are one of the greatest hopes in science for the treatment of cancer, and a consortium of Portuguese researchers is working on a key contribution: understanding how these cells from patients themselves, modified in the laboratory to recognize and attack only cancer cells, can work better . In partnership with the Portuguese Institute of Oncology (IPO) in Porto and the UCIBIO research unit of the Faculty of Sciences and Technology of the NOVA University of Lisbon (NOVA FCT), the biotechnology and regenerative medicine company Stemmatters leads the CAR T Matters consortium. But what are these CAR T cells and how do they work against cancer?

It all starts with T cells or T lymphocytes, a type of white blood cell whose function is to destroy cancer cells or cells that have been infected by any type of harmful virus or bacteria. Through genetic modifications in the laboratory, it is possible to make them find a specific therapeutic target — called an antigen or biomarker — that is present in the tumor, but that is not identified in any other healthy cell so that the latter cells remain unharmed.

Initially, cells are collected from the patient for a comprehensive analysis in search of these biomarkers , which are “signals” in the blood, tissues or any affected part of the body and which allow us to know more about the characteristics of the tumor.

From here, it becomes possible to identify the best targets to direct CAR T cell treatments to and, at the same time, understand what type of therapies can be administered. With CAR T therapy, tumors can be directly weakened , which provides stability or even the end of the signs of disease in patients.

“This is a new challenge in genetically manipulated T cells, to recognize specific targets in the tumor”, explains glycoimmunology specialist and member of the research group Paula Videira to Observador. At this precise moment, Portugal does not yet have the capacity to produce this type of cells autonomously, needing to “get it abroad” to begin research. However, “ways to better control the activation of T cells” are still needed, that is, the immune system’s response , continues the UCIBIO researcher. The goal is to ensure that this response is not “exacerbated”, “which is also not good” — and “to try to see molecules that allow us to understand how to control the activity of these lymphocytes”.

CAR T cells are not something that “can be stored in a box and sold at the pharmacy”, stresses Paula Videira. “We have to obtain T cells from patients, which are genetically manipulated to have a specific receptor that will recognize a specific target in the tumor”, she adds. Thus, the role of the UCIBIO team is to “ identify molecules” that can improve this therapy — “making it more effective and with fewer toxic effects” .

This is one of the biggest concerns associated with this treatment with CAR T cells, explains the researcher, indicating that before being modified, they serve “to kill other cells that are infected”. In this project, the group will “train” them to recognize an antigen (or biomarker) as specific as possible to fulfill this role, seeing the possibilities of “balancing the therapy so that it is effective”.

A major challenge in this research is obtaining biomarkers that are broad and represent a large portion of the population that has cancer. Therefore, “in this project, we are starting with more consensual biomarkers”, says the specialist. In addition, the “quantity and quality” of the cells extracted from the patient also proved to be a challenge, since the CAR T cells used for treatment “really have to come from the individual, to avoid rejection”, which ends up limiting the collection.