Gene editing allows cells to fine-tune their attack against cancer

  • A study tests CRISPR technology in 16 patients not only to eliminate genes, but also to insert new ones into immune cells

  • Although the clinical benefit in terms of patient response was limited, the technique represents a leap towards individualized treatments

A scientific team has managed to use the CRISPR gene editing technology to insert genes that allow immune cells focus your attack on cancer cells, potentially leaving the normals unharmed. This new approach that increases the efficacy of immunotherapy has been tested in a phase I clinical trial with 16 patients with various types of cancer (colon, breast and lung); This is an early proof of concept that demonstrates that the immune system of a patient can be rescheduled to recognize their own cancer.

The results were presented at the annual meeting of the Cancer Immunotherapy Society and are published in Nature magazine. The work is co-directed by the Spanish Antony Ribas, researcher at the Jonsson Comprehensive Cancer Center, of the University of California (UCLA), and professor of medicine at the same.

What does this technology consist of?

CRISPR/Cas9 is a biological tool which enables Modify the genome; Like a text editor, it is capable of manipulating the genome using a mechanism that “cuts and pastes” DNA sequences. The CRISPR technique has previously been used in humans to delete specific genes and allow the immune system to become more active against cancer.

In this new work, the researchers report the possibility of using CRISPR not only to delete specific genes, but also to insert new ones into immune cells, efficiently redirecting these to recognize mutations in the patient’s own cancer cells.

How does it work?

According to a UCLA news release, when reinfused into patients, these immune cells engineered with CRISPR preferentially target cancer and become the most represented immune cells there.

The immune system contains T cells that they can use specific receptors to find and kill cancer cells. Unfortunately, patients often don’t have enough of these immune cells to attack the cancer. completely and efficiently.

In addition, the receivers are different for each patient, so finding an efficient way to isolate them and insert them into immune cells is key code to generate a cellular therapy personalized against cancer.

The new research accounts for an efficient way to isolate these immune receptors of the patient’s own blood using technologies developed by the Ribas team in collaboration, among others, with the Nobel David Baltimore, and subsequently developed for testing by PACT Pharma.

personalized treatment

“It’s about a jump forward in the development of a personalized cancer treatment, in which the isolation of immune receptors that specifically recognize mutations from the patient’s own cancer are used to treat it,” says Ribas.

After the administration of chemotherapy, patients were infused with up to three of these immune cell preparations genetically edited, which involved the application of a total of 37 immune receptors to the 16 patients who participated in the research. The treatment resulted in stabilization of the disease in five of the 16 patients analyzed, while the other 11 experienced a progression, summarizes the magazine ‘Nature’. Only two patients showed adverse responses attributed to T cell therapy (both recovered quickly), while all experienced the expected side effects of chemotherapy treatment.

Related news

Although the clinical benefit in terms of patient response was limited, the study demonstrates the potential feasibility of this therapeutic strategy, says ‘Nature’. Remember that the authors highlight some limitations of his approach, as the time required to characterize potential antigens and to isolate, clone and test T cell receptors.

However, the researchers indicate that some of the processes improved over time. test duration and suggest that they are therefore possible future improvements.

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