Scientists have used the technology of 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 unscathed or at least less damaged from a treatment. The study has been published in the Nature medium and was conducted by Pact Pharma and the University of California, Los Angeles (UCLA).
To put it very simply, cancer occurs when certain cells in an organism mutate and divide uncontrollably. Every cancer is driven by a unique set of mutations, and every person has immune cells with receptors that can recognize those mutations to differentiate cancer cells from healthy ones. However, patients often do not have enough immune cells with the corresponding receptors to mount an effective response against their cancer.
In the phase 1 trial with CRISPR, the researchers identified the receptors from each patient, inserted them into immune cells that lacked them, and set about culturing them. The modified cells were then released into the bloodstream of the volunteer patients to attack the tumor.
researchers began with the separation of T cells, a component of the immune system with receptors that allow cancer cells to be detected, from the blood of sixteen patients with solid tumors, including colon, breast and lung. For 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 the genes for these receptors to T cells in the laboratory.
The scientists grew the modified cells until they had enough so that, in their opinion, it was enough to serve as a therapeutic dose. They then introduced the modified cells into each of the volunteers, who had previously been treated with several rounds of chemotherapy. The modified T cells traveled to tumors and infiltrated them.
As a result, the experimental therapy was able to stop the growth of the tumors in six of the patients, in another eleven people the cancer was seen to progress and two had side effects, with one having a fever and chills and another experiencing confusion. On the other hand, all the patients expected to experience the side effects of chemotherapy.
Stefanie Mandl, chief scientific officer of Pact Pharma and author of the study, initially suspected that response to therapy was limited because the patients’ cancers were so advanced when they enrolled in the trial. In addition, further tests revealed that some of the receptors chosen by the team could find the tumor, but did not have strong anti-cancer effects..
Bruce Levine, a professor of cancer gene therapy at the University of Pennsylvania, has said that the rapid identification of patients’ unique cancer receptors and the generation of personalized treatments is impressive, but that the challenge of choosing the correct receptors and actually capable of killing cancer cells.
Another obstacle is that it is proven that solid tumors are more difficult to treat with T cells than liquid tumors that affect 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 with solid tumors.
Here are other factors that can hinder the effectiveness of treatments, such as the fact that the cancer becomes complicated and ends up developing its own architecture, its own microenvironment and all kinds of defense mechanisms that ultimately make it more difficult to fight for the immune system.
Despite the limited results of the study, the researchers hope to find an effective way to use CRISPR against cancer, seeing that chemotherapy and radiation are effective for many patients, but kill both healthy and cancerous cells, and that’s not counting those who do not respond to treatment or end up relapsing. Personalized therapies open the door to selectively targeting only cancer cells.
At this time it seems that the use of CRISPR to combat solid tumors is far from being 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 really serve to create effective cells when fighting cancer.
