Mandl suspected that the response to the treatment was limited because the patients’ cancer was very advanced when they entered the trial. In addition, later tests showed that some of the receptors the team had chosen could find tumors but did not have strong anticancer effects.
Bruce Levine, Professor of Cancer Gene Therapy, University of Pennsylvania Scientist says the ability to quickly identify a patient’s unique cancer receptors and use them to generate tailored treatments is impressive profound. But the challenge is choosing the right drug that actually kills the cancer cells. “The fact that you can get these T cells into a tumor is one thing. But if they get there and do nothing, that’s pretty disappointing,” he said.
Solid tumors have also been shown to be more difficult to treat with T cells than liquid tumors or blood cancers, including leukemia, lymphoma, and myeloma. Therapies that use traditional genetic engineering (rather than Crispr) to modify a patient’s T cells have been approved for blood cancers, but they don’t work as well on solid tumors.
“The sooner a cancer becomes complex and develops its own structure, microenvironment and various defense mechanisms, then it becomes harder for the immune system to deal with it,” Great Ormond Street Institute for Children’s Research Waseem Qasim, professor of cell and gene therapy, said UCL Health.
While the findings are limited, the researchers hope to find a way to use Crispr to fight cancer, as the disease requires new treatments. Chemotherapy and radiation are effective for many patients, but they kill both healthy and cancerous cells. Tailored therapies may offer a way to selectively target a patient’s unique set of cancer mutations and kill only those cells. Also, some patients do not respond to traditional therapies, or their cancer recurs later.
But Crispr cancer research is still in its early stages. In a Penn study co-authored by Levine, three patients (two with blood cancer and a third with bone cancer) were treated with their own Crispr-edited T cells. The researchers removed three genes from these cells that made them better able to fight cancer. A preliminary study showed that the edited cells migrated to tumors and survived the infusion, but the Penn team has yet to publish findings on how patients fared after treatment.
Meanwhile, in London, Qasim’s team treated six critically ill children with leukemia using a donor’s Crispr-edited T cells. According to a recent study published in the journal Science, 4 out of 6 people were in remission after a month, allowing them to undergo stem cell transplantation. Of the four, two were in remission 9 and 18 months after treatment, respectively, while two relapsed after stem cell transplantation.
While there is still much to learn about how to improve these treatments, researchers like Qasim hope that new technologies like Crispr will eventually lead to better matches between treatments and patients. “There is no one-size-fits-all cancer treatment,” Kasim said. “What this type of study hopes to demonstrate is that every tumor is different. It’s a missile treatment, not a big bang approach.”
