Car-T-. Identify the key sources leading to T-cell depletion

A specialized group of proteins in the nuclei of our cells, called mSWI/SNF (or BAF) complexes, play a commanding role in activating or shutting down T cells, which are responsible for immune defense, according to a recent study from the Dana-Farber Cancer Institute. . By targeting some of these complexes, with gene editing technologies such as CRISPR or with targeted drugs, the phenomenon of ‘exhaustion’ of T cells could be reduced and their defense capacity is active long enough to be effective against the cancer, especially in CAR-T therapies.

21 MAR – A team from the Dana-Farber Cancer Institute (USA) has highlighted the “command role” played by a specialized group of proteins in the nucleus of our cells, the mSWI/SNF complex or BAF, both in activating T cells to attack tumor cells, and to lead to the ‘exhaustion’ of these immune cells.

The study, published by Molecular Cell, suggests that by targeting some of these complexes, with gene editing technologies such as CRISPR or with targeted drugs, the phenomenon of ‘exhaustion’ of T cells could be reduced and their ability to defend themselves is active long enough to be effective against cancer.

CAR-T therapies have opened a new era in the treatment of cancers, especially hematological ones. However, these treatments undergo a phenomenon that leads to a drastic ‘exhaustion’ of the ability to fight cancer. This mechanism, according to research conducted in recent years, would not be controlled by a single gene, but precisely by the coordination of many genes.

The mSWI/SNF complexes are large molecular ‘machines’ that glide along the genome like cursors along a computer-written text and at the point where they stop, they can open the DNA chain activating the genes, while when they disappear the DNA closes again by turning off the genes.

Source: Molecular Cell 2023

March 21, 2023
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