Mandl suspects that the response to the treatment was low because the patients’ cancer was so advanced by the time they enrolled in the trial. Also, later experiments showed that the receptors the group chose could find the tumor, but they had no anti-cancer properties.
Bruce Levine, a professor of cancer gene therapy at the University of Pennsylvania, says the ability to rapidly identify specific receptors in patients and develop therapeutic interventions using them is exciting. But the problem will be in choosing the right ones that kill cancer cells. “The fact that you can take T cells into a tumor is one thing. But when they get there and do nothing, it’s disappointing,” he says.
Solid tumors have also proven more difficult to treat with T cells than solid tumors, or blood cancers, which include leukemia, lymphoma, and myeloma. Medicines that use a natural gene (instead of Crispr) to modify patients’ T cells have been approved for leukemia, but do not work well for solid tumors.
“Once cancer becomes more complex and develops its structure and environment and various defense mechanisms, it becomes more difficult for the immune system to handle it,” says Waseem Qasim, professor of cell and gene therapy at Great Ormond. Street Institute of Child Health at University College London.
Although the results of this study were limited, researchers hope to find a way to use Crispr against cancer, because this disease requires new treatment. Chemotherapy and radiation help many patients, but they kill healthy and cancerous cells. Complementary therapies may offer a way to target specific changes in a patient and kill only those cells. Also, some patients do not respond to treatment, or their cancer returns later.
But it’s still early days for Crispr’s cancer research. In a study at the University of Pennsylvania that Levine collaborated on, three patients – two with leukemia and the third with bone cancer – were treated with their own T cells that had been modified with Crispr. Researchers removed three genes from those cells to make them better at fighting cancer. Early research showed that the transplanted cells migrated to the tumor and survived after transplantation, but Penn’s team did not publish what the patients found after treatment.
So far, Qasim’s team in London has treated six children with advanced leukemia, using Crispr-edited T cells from donors. Four of the six were in remission after a month, allowing them to receive stem cells, according to a study recently published in the journal. Science. Of the four, two remained in remission nine and 18 months after treatment, respectively, while two relapsed after stem cell transplantation.
While there is still much to learn about how to improve the treatment, researchers like Qasim hope that new technologies like Crispr will provide a better connection between treatment and patient. “There is no cure for cancer,” says Qasim. “What these kinds of studies hope to show is that every tumor is different. It’s a controlled treatment, rather than a big blast.”