In a new For Crispr, the scientists used gene editing to make personalized modifications to cancer patients’ immune cells to boost their tumor-fighting energy. . In a small study published today on magazine NatureA research group in the US showed the method to be feasible and safe, but only successful in a small number of patients.
Cancer arises when cells mutate and divide uncontrollably. Each cancer is driven by a unique set of mutations, and each has immune cells with receptors that can recognize these mutations and differentiate cancer cells from normal cells. But patients often don’t have enough cells that are immune to these receptors to produce an effective response against their cancer. In this Phase 1 trial, the researchers identified each patient’s receptors, inserted them into immune cells that lacked them, and further grew these modified cells. The enhanced immune cells are then released into each patient’s bloodstream to attack their tumor.
“What we’re trying to do is exploit each patient’s tumor-specific mutations,” said Stefanie Mandl, chief scientific officer at Pact Pharma and an author of the study. The company worked with experts from the University of California, Los Angeles, the California Institute of Technology, and the nonprofit Institute of Systems Biology in Seattle to design personalized therapies.
The researchers started by separating T cells from the blood of 16 patients with solid tumors, including colon, breast or lung cancers. (T cells are part of the immune system with these receptors.) For each patient, they identified dozens of receptors capable of binding to cancer cells taken from their own tumours. . The team selected up to three receptors for each patient and, using Crispr, added the genes of these receptors to that person’s T cells in the lab.
The scientists have grown enough edited cells to form what they hope will be a therapeutic drug. They then re-infused the edited cells into individual volunteers, who had previously been treated with multiple rounds of chemotherapy. Edited T cells migrate to tumors and infiltrate them.
In six patients, the experimental therapy stopped the growth of tumors. In the remaining 11 people, their cancer was more advanced. Two had modified T-cell therapy-related side effects — one had fever and chills, and the other was confused. Everyone in the trial expected side effects from chemotherapy.
Mandl suspects the response to the therapy has been limited because the patient’s cancer was very advanced at the time they signed up for the trial. In addition, subsequent tests showed that some of the receptors the team selected could detect tumors, but not have strong anti-cancer effects.
Bruce Levine, a professor of oncology gene therapy at the University of Pennsylvania, says the ability to rapidly identify a patient’s unique cancer receptors and create tailored treatments using them is key. very impressive. But the challenge will be choosing the right one that actually kills cancer cells. “It’s one thing that you can get those T cells into the tumor. But if they go there and don’t do anything, that’s disappointing,” he said.
