Ordered to survive
The edited immune cells survived and multiplied in the tumors
The researchers injected immune cells genetically modified using CRISPR technology into cancer tumors. After extracting them a few months later, the authors found that the cells were intact and even increased their numbers. An article about the discovery was published in the journal Science (Stadtmauer et al., CRISPR-engineered T cells in patients with refractory cancer).
"Our data from the first three patients included in the clinical trial demonstrate two important things that, as far as we know, no one has ever shown before. Firstly, we can successfully perform multiple changes to the genome of cells with high accuracy during their creation, which allows them to survive much longer than all previous analogues. Secondly, so far these cells have demonstrated a stable ability to resist the spread of tumors," notes Karl Jun, MD, professor at the University of Pennsylvania and co–author of the work.
The approach in this study is closely related to CAR-T-cell therapy, during which the patient's immune cells are taken and "reprogrammed" to fight cancer, but it has some key differences. As with this type of therapy, the researchers in the new work began by collecting the patient's T cells from the blood. However, instead of arming these cells with a receptor against a protein such as CD19, the team first removed three genes using the CRISPR/Cas9 tool.
The first two changes removed the natural T-cell receptors, replacing them with synthetic T-cell receptors that allow them to search for and destroy tumors. The third edit removed PD-1, a natural checkpoint that sometimes prevents T cells from doing their job.
After that, the researchers injected the resulting cells into the tumors of three patients and showed that synthetic structures were able to multiply in them, and all their "offspring" retained three edited genes. The researchers then made a fourth change in the genome using a lentivirus to create a synthetic receptor in the cells that allows them to target the NY-ESO-1 antigen.
Previously published data showed that such cells usually survive less than a week, but the newly modified T-lymphocytes were able to live in a cancerous tumor for a very long time - up to nine months. And although none of the three patients got better during the clinical trial, the scientists managed to avoid possible side effects of such therapy.
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