This Personalized Crispr Therapy Is Designed to Attack Tumors

Mandl suspects the response to the therapy was limited because the patients’ cancers were already very advanced by the time they enrolled in the trial. Also, later tests revealed that some of the receptors the team chose could find the tumor, but didn’t have potent anticancer effects.

Bruce Levine, a professor of cancer gene therapy at the University of Pennsylvania, says the ability to rapidly identify patients’ unique cancer receptors and generate tailored treatments using them is impressive. But the challenge will be in picking the right ones that actually kill cancer cells. “The fact that you can get those T cells into a tumor is one thing. But if they get there and don’t do anything, that’s disappointing,” he says.

Solid tumors have also proven more difficult to treat with T cells than liquid tumors, or blood cancers, which include leukemia, lymphoma, and myeloma. Therapies that use traditional genetic engineering (rather than Crispr) to modify patients’ T cells have been approved for blood cancers, but they don’t work well on solid tumors.

“As soon as the cancer gets complicated and develops its own architecture and a microenvironment and all sorts of defense mechanisms, then it becomes harder for the immune system to tackle it,” says Waseem Qasim, professor of cell and gene therapy at the Great Ormond Street Institute of Child Health at University College London.

While the results of the study were limited, researchers hope to find a way to use Crispr against cancer, because the disease demands new treatments. Chemotherapy and radiation are effective for many patients, but they kill healthy cells as well as cancerous ones. Tailored therapies may offer a way to selectively target a patient’s unique set of cancer mutations and kill only those cells. Plus, some patients don’t respond to traditional therapies, or their cancer comes back later.

But it’s still early days for Crispr cancer research. In a study at the University of Pennsylvania that Levine coauthored, three patients—two with blood cancer and the third with bone cancer—were treated with their own Crispr-edited T cells. Investigators had removed three genes from those cells to make them better at battling cancer. A preliminary study showed that the edited cells migrated to the tumor and survived after infusion, but the Penn team hasn’t published findings on how the patients fared after the treatment.

Meanwhile, Qasim’s team in London has treated six children who were seriously ill with leukemia, using Crispr-edited T cells from donors. Four of the six went into remission after a month, which allowed them to receive a stem cell transplant, according to a study published recently in the journal Science. Of those four, two remain in remission nine months and 18 months after treatment, respectively, while two relapsed following their stem cell transplant.

While there’s still much to learn about how to improve these treatments, researchers like Qasim hope that new technologies like Crispr will ultimately yield a better match between therapy and patient. “There’s no one-size-fits-all treatment for cancer,” says Qasim. “What these kinds of studies hope to demonstrate is that each tumor is different. It’s a guided missile type of treatment, rather than a big blast approach.”