Electric jolt helps T-cells battle cancer
A promising new class of cancer treatments recruits the cells in our blood to fight tumors, using powerful gene-editing tools to transform a type of white blood cell — called a T-cell — from an immune cell that normally targets bacterial or fungal infections into a living cancer drug.
The genetic alterations could boost immune systems to successfully fight cancers on their own. Researchers remove T-cells from patients and slip new genes into the cells. After clinicians return the modified T-cells to patients, the cells, like microscopic bloodhounds, lead the immune system on the hunt for tumors.
“We’re living in an amazing moment in cancer immunotherapies,” said Alexander Marson, a microbiology and immunology professor at the University of California, San Francisco.
In 2017, the Food and Drug Administration began approving genetically altered immune cells for small groups of patients, such as those with aggressive non-Hodgkin lymphoma or a rare form childhood leukemia. Other experimental trials, involving cancers such as myeloma and melanoma, show encouraging results.
But further developments have been slowed, with a bottleneck arising not from red tape but demand. Delivery systems able to insert new genes into immune cells are in short supply.
Disabled viruses, which inject genes into cells like a shot from a syringe, are the current standard. Just a few biotechnology companies, equipped with expensive manufacturing systems, can produce the viral vectors. Wait times for new viruses can be as long as several years, as James Wilson, who directs the gene therapy program at the University of Pennsylvania’s Perelman School of Medicine, told the New York Times in November.
Marson and his colleagues have developed a new, faster method to reprogram T-cells, as they described Wednesday in the journal Nature. Rather than relying on viruses to deliver the genetic package, researchers jolted T-cells with electricity. The shock relaxed the membranes that surround the cells, making them receptive to new genetic material.
“It’s a turning point,” said Vincenzo Cerundolo, director of the Human Immunology Unit at Oxford University, who was not involved with this study. “It is a game-changer in the field and I’m sure that this technology has legs.” He predicts cheaper therapies and much faster development times — as swiftly as a week, rather than the months required to manufacture a virus.
In the new research, Theodore Roth, a doctoral student in Marson’s lab, performed thousands of experiments in quick succession to identify the best way to zap new genes into T-cells.
The method’s efficiency varied, depending on the donor cells and the targeted genes. In cells from healthy volunteers, the most successful group, the new genes integrated with as many as 35 percent or 40 percent of cells.
Study co-author Kevan Herold, an endocrinologist and immunologist at Yale University, said it is too early to discuss cost, except to note that the therapies are not inexpensive.
Current costs for gene therapy can be as high as $1 million for rare diseases. Treatment for more common diseases also can be expensive, with bills running in the six-figures.