Sci Trans Med: New switch can regulate CAR-T cell activity

January 7, 2021 // -- CAR T cells are an effective cell-based immunotherapy that has been a great success in treating certain advanced cancers, but poses a significant risk of toxic side effects.
to this, scientists at the Dana-Farber Cancer Institute and Massachusetts Cancer General Hospital created a molecular "ON-OFF" switch to regulate the activity of CAR T cells, immunomodulation immune cells that identify and attack tumor cells.
once given, these "living drugs" multiply and kill tumor cells within weeks to months.
, however, can cause life-threatening inflammatory reactions that are difficult to control.
(Photo: www.pixabay.com) Scientists report in the journal Science Translational Medicine on the development of switchable CAR T cells that can be turned on or off by giving commonly used anti-cancer drugs.
in the lab, the researchers were able to quickly and reversiblely shut it down by using the drug, and then CAR T cells resumed their anti-tumor activity.
, switchable cell therapy may allow patients to adjust their daily CAR T cell activity, potentially reducing toxic side effects.
, our goal was to build less difficult cancer treatments.
we are pleased to have the potential to turn this research into a clinical application.
"s first author, Dr. Max Jan.
CAR-T cells are produced by collecting immune T cells from the patient and reprogramming them in the laboratory, resulting in a fine-tuned subject molecule called CAR (used to chime antigens) that identifies unique proteins on the patient's cancer surface.
cells.
CAR T cells are engineered in the lab and returned to the patient, circulating in the body and returning to cancer cells by binding to unique surface proteins that are engineered to identify them.
this binding event stimulates immune attacks, the destruction of cancer cells, and the proliferation of CAR T cells.
, however, the disadvantage is that uncontrolled proliferation of CAR T cells can sometimes trigger cytokine release syndrome (CRS), an inflammatory factor that releases in the body and can lead to a variety of toxicity, from mild fever to life-threatening organ failure.
current management of these toxic reactions relies on the support of intensive care units and drugs including immunosuppressive corticosteroids, and many researchers are trying to develop ways to control car T cell activity to prevent these toxic side effects.
can be very effective therapies, but they can also be highly toxic and can lead to high morbidity and mortality rates," said Albert, director of the Department of Oncology.
are hard to control at the moment.
" CAR T cell therapy is the most successful in blood cancer and has been approved for three CAR T-related therapies: Kymriah for children and adolescents with B-cell pregenital acute lymphoblastic leukemia (ALL), Kymriah and Yescarta for adults with diffuse large B-cell lymphoma;
, scientists are working on a range of different approaches aimed at overcoming many clinical barriers, including the treatment of toxicity, to extend THE treatment to other blood cancers and solid tumors.
() Source: Scientists create ON-OFF switches to control CAR T cell activity Source: M. Jan el al., "Reversible ON- and OFF-switch chimeric antigen receptors controlled by lenalidomide," Science Translational Medicine (2020). stm.sciencemag.org/lookup/doi/ ... scitranslmed.abb6295