CAR-M era begins as Carisma doses first patient
Last month, doctors at the Abramson Cancer Center in Philadelphia inserted a needle into a patient with an untreatable tumor and began drawing blood into a machine.
The machine filtered out everything but a specific set of immune cells that were then packaged, put on a plane and shipped, still warm, to a facility in Sunnyvale, CA. Over 24 days, technicians expanded the cells, armed them with a new kind of receptor and sent them back, now cryogenically frozen, on a plane to Philadelphia to be infused back into the patient.
It’s a familiar process. A few details aside, it’s played out thousands of times over the past half decade as patients with deadly blood cancers received CAR-T treatments, potentially life-saving infusions of genetically turbocharged T cells. But for the first time, developers used a different immune cell, one they hope can unlock a whole new set of patients and incurable tumors: macrophages.
Carisma Therapeutics, the University of Pennsylvania spinout, announced today that they had dosed their first patient with CAR-macrophages, or what they call CAR-M. Relying on a bubbly immune cell that eats pathogens and often gathers around solid tumors, they hope it can bring the benefits of cell therapy into places where CAR-T has consistently failed.
“CAR-T therapies have made huge advances in the field of [blood cancers], but there are major limitations to utilizing the same technology in solid tumors,” Joshua Bauml, an oncologist at Penn Medicine and lead investigator on the study, told Endpoints News. “And I think that this trial aims to overcome some of those in a very clever way.”
Biotechs and academic researchers have managed to make CAR-Ts with receptors that go after several different blood cancers, including lymphoma and multiple myeloma. But efforts to apply T cells in solid tumors have failed, in large part because many such tumors have mechanisms to keep T cells from infiltrating their environment and destroying cancer cells.
Those environments, though, are often swarming with macrophages. That’s actually a bad thing: There are multiple types of macrophages and tumors rely on ones that suppress the immune system, effectively giving the cancer a walled-off compound in which to thrive.
But nearly a decade ago University of Pennsylvania hematologist Saar Gill and a graduate student, Michael Klichinsky, figured out that if you attached a CAR onto a macrophage, those macrophages can enter the tumor’s environment like a Trojan horse. There it both directly eats up the tumor and sends out signals that turn bad macrophages into good macrophages that can kill cancer cells and recruit other immune cells to join the brigade.
Or at least it did in animal models. The new trial is testing to see whether those results can translate into humans, beginning with 18 patients who have cancers that express HER2 and have exhausted other options.
Carisma chose to start with HER2 because there’s already a swath of treatments that target the receptor, CMO Debora Barton said. It helps standardize an otherwise highly experimental procedure.
“We don’t want to add any variability,” she told Endpoints.
The first group of patients will receive 5 billion cells in 3 different infusions over 5 days to ensure nothing goes wrong. If that goes well, the second group will receive all the cells at once. Barton, though, said they have good evidence to suggest the therapy is safe. It doesn’t require the same intense conditioning regimen that CAR-T therapies do, and they don’t think it will trigger the cytokine release syndrome, the dangerous immune over-reaction that CAR-T can stimulate.
Barton isn’t promising the near-curative impact that the first CAR-T studies showed. Instead, they’re hoping to simply show that it’s safe, that the CAR-Ms are getting into the environment around the tumor and that they’re having some effect.
The study also serves as a test run for the month-long, cross-country process manufacturing needed to make the CAR-Ms. Carisma has checked all the logistical boxes, she said, but making a cell therapy is never an easy task. If it runs smoothly and proves safe, Carisma hope to move forward with a swath of CAR-M therapies for other tumors and other antigens.
“It’s a whole world of logistics that we need to get in place, and we have it in place, but you know there are snowstorms and everything can happen,” Barton said. “Everything can go wrong and we’re taking all measures.”