Scientists used technology Clustered regularly interspaced short palindromic repeats (CRISPR) to insert genes into immune cells and make them focus on attacking cancer cells, leaving the door open for healthy cells to emerge unharmed or at least less damaged by treatment. The study was published in Nature and was conducted by Pact Pharma and the University of California, Los Angeles (UCLA).

In very simple terms, cancer occurs when certain cells in the body mutate and divide uncontrollably. Each cancer is driven by a unique set of mutations, and each person has immune cells with receptors that can recognize these mutations and distinguish cancer cells from healthy ones. However, patients often do not have enough immune cells with the appropriate receptors to mount an effective response against their cancer.

In a phase 1 study with CRISPR the researchers identified the receptors from each patient, inserted them into immune cells that lacked them, and set about cultivating them. The modified cells were then released into the bloodstream of volunteer patients to attack the tumor.

researchers it began by separating T cells, which are part of the immune system with receptors that allow the detection of cancer cells, from the blood of sixteen patients with solid tumors, including colon, breast, and lung. In each patient, dozens of receptors capable of binding to cancer cells extracted from their own tumors were identified. From there, the researchers selected up to three receptors for each patient and used CRISPR to add genes for those receptors to T cells in the lab.

The researchers grew the modified cells until there were enough of them to make what they believed to be a therapeutic dose. They then introduced the engineered cells into each of the volunteers who had previously been treated with several cycles of chemotherapy. The modified T cells traveled to and infiltrated the tumors.

As a result, the experimental therapy was able to stop the growth of tumors in six patients, in another eleven the cancer progressed and two had side effects, with one having fever and chills and the other experiencing confusion. On the other hand, all patients expected side effects of chemotherapy.

Stefanie Mandl, Chief Scientific Officer of Pact Pharma and author of the study, they initially suspected that the response to the therapy was limited because the patients’ cancer was so advanced when they were enrolled in the study. In addition, further tests revealed that some of the receptors the team selected were able to find the tumor but did not have strong anti-cancer effects..

Bruce Levine, a professor of cancer gene therapy at the University of Pennsylvania, said that quickly identifying patients’ unique cancer receptors and creating personalized treatments is impressive, but that choosing the right receptors that are actually capable of killing is difficult. cancer cells.

Another obstacle is that solid tumors have been shown to be more difficult to treat with T cells than liquid tumors affecting the blood, such as leukemia, lymphoma and myeloma. Therapies that use traditional genetic engineering to modify T cells, without CRISPR, have been approved to treat cancers detected in the bloodbut they have not been shown to be as effective in solid tumors.

Here are other factors that can hinder the effectiveness of treatment, such as the fact that cancer gets complicated and eventually develops its own architecture, its own microenvironment, and all kinds of defense mechanisms that eventually make it harder for the immune system to fight. .

Despite the limited results of the study, the researchers hope to find an effective way to use CRISPR against cancer, as chemotherapy and radiation are effective for many patients, but they kill both healthy and cancer cells, not counting non-responders. to treatment or end up with a relapse. Personalized therapies open the door to selectively targeting only cancer cells.

Currently, the use of CRISPR in the fight against solid tumors seems far from a complete solution, but everything indicates that an important step has been taken. If these results are confirmed, the challenge would be to find the receptors that actually serve to create effective cancer-fighting cells.