StemCell Therapy

Xconomy National

Its a struggle that comic-book fans know well. Ordinary people, bestowed with super powers from a spider bite or gamma rays, struggle to harness their own abilities.

T cells, key soldiers of the immune system, are wrestling with new-found super powers, too. Certain T cells hunt down invasive viruses, bacteria, and the bodys own bad seedsthe early signs of cancer. But cancer has ways of evading the immune system, so researchers are engineering T cells to give them extra cancer-fighting talents. These so-called CAR-T treatments, administered experimentally in clinical trials, have helped dozens of patients with otherwise untreatable blood cancers.

Now the fields first-ever regulatory approval is looking like a strong possibility, making this a watershed year for CAR-T therapy. But the supercharged T cells remain an enigma. Experts are wrestling with the super-hero problem that threatens to limit their usefulness: How can the cells be engineered to kill cancer without running amok?

Its more important than anything else to keep learning how CAR-T cells work and how they potentially carry risk, says Amir Fathi, an assistant professor of medicine at Harvard Medical School. As director of the leukemia program at Massachusetts General Hospital in Boston, Fathi treats patients with experimental CAR-T therapies.

(CAR-T stands for chimeric antigen receptor T cells, which describes the modification that picks up the signals of tumor cellssensitive T cell spyware, if you will.)

With Kite Pharma (NASDAQ: KITE) of Santa Monica, CA, nearly ready to ask the FDA to review its CAR-T axicabtagene ciloleucel as a treatment for adults with non-Hodgkin lymphoma (NHL), the fields first-ever approval could be months away. International drug giant Novartis (NYSE: NOV) might not be far behind, with a CAR-T for pediatric patients with acute lymphoblastic leukemia (ALL).

For now, the Kite and Novartis products are meant for narrow groups of patients who have failed to improve with other therapies, including chemotherapy and bone-marrow transplant. Their doctors are thrilled to have the first generation CAR-Ts. The patients whom these trials are targeting, theyre typically highly refractory, they have no options left, says Krishna Komanduri, director of the Sylvester Cancer Center Adult Stem Cell Transplant Program at the University of Miami.

But is a last-ditch lifeline for patients with severe cases of two blood cancers the ceiling for CAR-T? Doctors, patients, and investors who have poured billions of dollars into the field have much higher hopes that the living cells will stand alone as long-term treatments, even cures, not just improvements upon current standards or temporary bridges to get patients healthy enough for bone-marrow transplantswhich are fraught with risks, too.

The risk of dying from transplants has come down under 20 percent in recent years, which is still higher than the overall death risk from CAR-T. But transplants are proven to cure cancer; CAR-T therapy has a long way to go. I think we need to see no evidence of disease [in patients] for several years, ideally three to five, before even comparing it to transplant, says Vinay Prasad, a blood cancer specialist at Oregon Health & Science University in Portland, and a critic of what he sees as a rush to useand pay forexpensive new medicines and procedures.

Ambitions also include eventual treatment of more common solid tumorsbreast, colon, and lung, for example. But the obstacles in realizing those ambitionsunderstanding CAR-Ts potentially deadly side effects, training a wide range of medical staff, and convincing healthcare insurers that the treatments are worth paying forwill not be easy to surmount. As Komanduri notes, bone marrow transplants from donors have been known for decades to cure lymphoma, but inadequate Medicare coverage has held the field back. The endgame should not be proving that a technology works in the clinical trial setting and securing FDA approval, says Komanduri, but ensuring we have a framework that maximizes access to curative treatments in a sustainable way.

SIDE EFFECTS, DEATHS, AND RELAPSES

As noted in Xconomys searchable CAR-T clinical results database, many programs have had stunning early results. More than 80 percent of leukemia patients, for example, have shown no signs of cancer a few weeks after treatment. Relapse rates climb after a few months in most studies. Lymphoma patients have had lower rates of remission, but in the Kite Pharma program that could be up for approval this year, the rates have stayed stable for six monthsa big deal in the CAR-T world.

Significant side effects are likely to limit CAR-T therapy to major treatment centers that can handle their unpredictability and sudden severity. Doctors working on CAR-T studies say theyre getting a handle on one common side effect, called cytokine release syndrome, with steroids and other drugs. But CAR-T treatments are also causing Next Page

Alex Lash is Xconomy's National Biotech Editor. He is based in San Francisco.

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Possible Cures. Mystery Deaths. Daunting Costs. Can CAR-T Be Tamed? - Xconomy

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