Advanced ways to turn the immune system against cancer

Cellular therapies, such as CAR-T Cells and gene therapies, are in Einstein's corridors, whether in laboratories or in clinical practice

One of the features that make cancer such a complex disease is its ability to “hide” from the immune system. Because they carry similarities with healthy tissue, tumor cells are often not identified as threats by different lines of body defense, such as T lymphocytes and Natural Killers, or NKs.

But cell therapies such as CAR-T Cells can break this indolence of the immune system, with significant results including in the control of hematological cancers in advanced stages, when other strategies have failed. At Einstein they are applied and studied in different lines.

To incorporate such complexity, it is essential to have a trained team, a state-of-the-art clinical infrastructure and an equipped and operational research center. “At Einstein, we have all this. So much so that phase 1 research for CAR-T Cell is entirely carried out within the organization,” points out Lucila Kerbauy, Medical Coordinator, Advanced Cell Therapies, Einstein Cell Therapies Department.

That is, the collected T cells are not taken to another location (or another country) to be manipulated; it all happens in Einstein's own Clean Room. Only the viral vector used in that phase 1 study comes from a supplier company, but the organization already conducts studies to develop its own vectors. The examinations and treatment application, of course, also take place in the hospital.

This means that Einstein is one of the few centers in Brazil capable of administering CAR-T Cells and, above all, of studying this technology. No wonder, the organization received grants from the Support Program for the Institutional Development of the National Health System (PROADI-SUS) to develop a Brazilian CAR-T Cell, made available for SUS patients during the clinical study, which may save resources and expand access. It was the first center authorized by Anvisa to conduct Brazilian studies using CAR-T Cells for lymphomas and leukemias.

Einstein also has projects to create other CAR-T Cells, for different targets and cancers. And CAR-NK Cells too.

“Natural Killer is another cell that can help fight cancer. It has the advantage of not causing graft disease against the host, so it would not need to be extracted from the patient, which is interesting to simplify treatment and make it accessible,” says Kerbauy. "On the other hand, it is more challenging to manipulate it so that it expresses the desired receptors and becomes a CAR-NK,” she adds.

Along the same lines, science seeks to make additional changes to the CAR-T Cells so that they no longer express proteins that would be recognized as threats if they were infused into other patients. And also to make them even more potent. All these lines are targets of study at the Teaching and Research Center – so professionals linked to the organization have the possibility to get in touch with this cutting-edge technology.

Currently, CAR-T Cells are only applied to hematological cancers, but there is a global search for solutions that make them effective against solid tumors as well. One of the targets studied in Einstein aims precisely at this.

"Another future line, which we evaluate internally, is to develop RNA molecules that generate changes in lymphocytes and other cells of the immune system in a patient’s body, instead of doing it all outside," says Luiz Vicente Rizzo, Research Director at Einstein.

This logic, driven by the success of RNA vaccines during the Covid-19 pandemic, would greatly simplify treatment. Possibly, the person would receive from time to time doses of a medication that would stimulate changes in the defense cells capable of making them bind to the cancer and destroy it.

“When we look back, we will see that Medicine has been revolutionized by this ability to work with RNA molecules. So we are already looking at this today at Einstein”

Patricia Severino, Einstein researcher