By Nadia Halim, Damon Runyon Science Writer

After mounting excitement in the last five years over a revolutionary approach to cancer therapy, patients are one step closer to seeing CAR T immunotherapy approved by the FDA for acute lymphocytic leukemia (ALL), the most common type of childhood cancer. The FDA’s 10-member advisory panel unanimously recommended Novartis Pharmaceuticals' experimental therapy (CTL019) be approved for use in children and young adults whose leukemia doesn't respond to traditional treatments — approximately 600 patients per year in this country.

“If approved, this not only marks the first gene transfer therapy in the US, it is also a major milestone for immunotherapy for cancer, for approvals in pediatrics, and for approvals in personalized therapy. In my experience, important government committees like this tend to be conservative and really tease out risk:benefit ratios when considering such recommendations. However, these scientists used exuberant language saying, ‘this is the most exciting thing I’ve seen in my lifetime.’ A patient’s father also was a strong advocate, and pulled heartstrings when he finished with  ‘if you want to see what a cure looks like, she’s standing right next to me’,” said Marcela V. Maus, MD, PhD, Damon Runyon-Rachleff Innovator at Massachusetts General Hospital.

This enthusiasm is based on the clinical trial’s indisputable success. In a pivotal study of 68 children at 25 medical centers around the world, 83 percent of patients went into complete remission, even though they had previously relapsed with conventional treatments, according to Novartis’ data. After six months, 75 percent of the patients who responded remained cancer-free. Since the long-term side effects are unknown, the FDA panel recommended that all patients who receive the treatment be monitored for 15 years.

However, CAR T (chimeric antigen receptor T cell) therapy is vastly different from traditional small molecule drugs, which are manufactured and characterized in big batches. Each treatment is created specifically for an individual patient in a complex multistep process. Key immune cells called T cells are harvested from a patient's blood, frozen, and then sent to a lab. A gene is inserted into the T cells that prompts them to grow a “receptor” that targets a special marker found only on the blood cancer cells. Millions of copies of the modified T cells are grown in the lab and then sent back to the hospital to be injected into the patient's bloodstream where they can find and destroy cancer cells. Doctors call it a "living drug" — permanently altered cells that continue to multiply in the body to fight the disease.

Such a complex system for making personalized treatments is likely to drive up their cost, and the next big hurdle (assuming an FDA approval this fall) is to win over insurers. The one-time treatment is predicted to cost as much as $600,000.

“Two major obstacles that remain are price and the ability to return product to patients faster than the reported 1 month turnaround time and with better reliability than the greater than 10% production failure rate. If patients are dying because the cells take too long to produce, cannot be produced, or are prohibitively expensive, then the deserved excitement of patients, care providers, researchers, and pharma will be short-lived,” cautions Marco L. Davila, MD, PhD, Damon Runyon Clinical Investigator at the H. Lee Moffitt Cancer Center and Research Institute.

Damon Runyon Scientists at the Forefront of Immunotherapy Research

Despite the hurdles ahead, many researchers and several companies are working on CAR T treatments for a range of cancers from non-Hodgkin lymphoma and multiple myeloma to solid tumors. Marco is developing CAR T treatments for malignancies including leukemias and lymphomas, which affect older adults and immunocompromised individuals.

Marcela is working on engineering CAR T therapies targeting brain tumors such as glioblastoma, as well as other cancers. Last week, published results from her clinical trial with glioblastoma patients showed for the first time that CAR T cells crossed the blood-brain barrier to reach tumors and appeared to be safe. Her lab is working on next steps such as combining CAR T cells with other drugs to increase the potency of this treatment to shrink tumor size.

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Links:
Human CAR-T Cell Glioblastoma Trial Generates Clues for Improving Treatment, Genetic Engineering and Biotechnology News
http://www.genengnews.com/gen-news-highlights/human-car-t-cell-glioblastoma-trial-generates-clues-for-improving-treatment/81254675

'Incredibly Exciting': CAR T Cells as 'Living Drugs’
Medscape
http://www.medscape.com/viewarticle/882968