Scientists are now developing alternative strategies for producing new types of CAR-T treatments.
Progress in today’s hottest area of cancer research continues, following the FDA’s recent approval of the first two chimeric antigen receptor (CAR) T-cell therapies – Novartis’s Kymriah for acute lymphoblastic leukemia (ALL) and Kite’s Yescarta for large B-cell lymphomas.
Scientists are now developing alternative strategies for producing these patient-specific treatments. Findings from a recent clinical trial, for example, could open the door to a larger variety of CAR-T therapies that work in different ways to help patients who don’t respond to existing treatments.
Led by researchers at the National Cancer Institute and Stanford University, the Phase I. dose-escalated clinical trial focused on patients under 30 years old with relapsed/refractory ALL. The study, recently published in Nature Medicine, is the first in humans to show the safety and effectiveness of a new CAR therapy targeting strategy.
This novel treatment programs a patient’s immune system T cells to go after the CD22 antigen in cancer cells rather than the CD19 antigen targeted by existing CAR therapies. In so doing, the team may have found a key to effective new treatments and treatment combinations that benefit a wider range of patients. “This trial gives hope to the idea that there may be another similar, very potent treatment” to complement anti-CD19 CAR therapies, said Crystal Mackall, M.D., associate director of Stanford’s Cancer Institute.
Treatment of Last Resort
ALL is the most common childhood and adolescent cancer. Chemotherapy alone is usually enough to halt the disease, but a percentage of patients receiving chemo or a bone marrow transplant either don’t respond at all or relapse after a short period of remission.
Anti-CD19 CAR T-cell therapies were approved for that subset of patients who have no other options. And the new experimental therapy tested in the NCI/Stanford trial goes one step further – it was designed to fight cancers that have eluded even these powerful new anti-CD19 CAR therapies. Of 21 total patients in the study, 15 had previously either relapsed or failed to respond to an anti-CD19 CAR T-cell treatment because their cancer cells stopped expressing enough antigen to trigger the immune response.
Although the trial was small, the results were encouraging, echoing the dramatic remission rates of the original groundbreaking CAR T-cell trials of recent years. Among the 21 participants, complete remission rates reached 80% for certain groups. The median remission duration was six months, with several patients still experiencing a complete remission nearly two years after treatment.
“This is the first time that we’ve seen response rates anything like we achieved when we were first testing the CD19 CAR T therapy,” Mackall said. “We were all a little worried we wouldn’t find anything comparable.”
The New Twist
Due to the large number of investigational anti-CD19 CAR T therapies moving through the development pipeline, a major question in immunotherapeutics is whether or not there are other proteins on cancer cells that could be similarly targeted with comparable therapeutic effect. The NCI/Stanford CD22 study provides the first evidence that there may be.
Lead investigator Terry J. Fry of the NCI first announced the team’s preliminary findings in February 2017 at the annual meeting of the American Society of Hematology. “This is the first successful salvage CAR therapy for CD19-negative, B-cell ALL,” he said in a briefing. “The preliminary experience suggests comparable potency to anti-CD19 CAR therapy. We have been able to show that you can give a second CAR therapy that is directed against a different antigen and have it be safe and effective.”
While researchers seek answers to key questions about the best uses for anti-CD22 CAR T therapies, they will also be exploring the use of anti-CD19 and anti-CD22 targeting approaches in tandem in hopes of overpowering even the most adaptable forms of cancer.
Michael MacRae is an independent technical writer based in Portland, OR.
Read more about Cell Therapy on AABME.org.