Personalised cell ‘editing’ used to treat cancer patients for first time: Study

Scients have, for the first time, used CRISPR technology to insert genes that allow immune cells to attack cancer cells, potentially leaving normal cells unharmed and increasing the effectiveness of immunotherapy.
The CRISPR gene editing technique has been previously used in humans to remove specific genes to allow the immune system to be more activated against cancer.
The research, published in the journal Nature, used CRISPR to not only take out specific genes, but also to insert new ones in immune cells efficiently redirecting them to recognise mutations in the patient’s own cancer cells.
When infused back to patients, these CRISPR-engineered immune cells preferentially traffic to cancer and become the most represented immune cells there, the researchers said.

The human immune system has specific receptors on immune cells that can specifically recognise cancer cells and differentiate them from normal cells.
These are different for every patient, so finding an efficient way to isolate them and insert them back into immune cells to generate a personalised cell therapy to treat cancer is key to making the approach feasible on a large scale.
Patients had the expected side effects from chemotherapy (Getty Images/Thinkstock)
The researchers found an efficient way to isolate these immune receptors from a patient’s own blood.
After isolation, the immune receptors are used to redirect immune cells to recognise cancer using CRISPR gene editing.
“This is a leap forward in developing a personalised treatment for cancer, where the isolation of immune receptors that specifically recognise mutations in the patient’s own cancer are used to treat the cancer,” said Antoni Ribas from the University of California, Los Angeles (UCLA), US.
“The generation of a personalised cell treatment for cancer would not have been feasible without the newly developed ability to use the CRISPR technique to replace the immune receptors in clinical-grade cell preparations in a single step,” said Ribas, corresponding author of the research paper.
The researchers report treating 16 patients with a variety of solid cancers including colon, breast and lung cancers.

The patients had immune cells isolated from their blood based on their binding to capture reagents that displayed up to 350 mutations from the patient’s own cancer, for a total of over 5000 mutations being targeted across 34 flavours of HLA subtypes of the immune system.
The genes of the immune receptors that allowed the immune cells to specifically recognise the cancer mutations were then sequenced, totaling 175 newly isolated cancer-specific immune receptors.
They were then inserted back into the patient’s own immune cells using a one-step CRISPR editing, which included the knock-out of the exing immune cell receptors and knock-in of the immune receptors that could redirect those cells to specifically recognise mutations in their cancer.
Patients had the expected side effects from chemotherapy, and two patients had potential side effects from the gene edited cells, one with fevers and chills and the other with confusion, both recovering promptly, the researchers said.
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