Bringing CARs to Market: Novel T-Cell Therapies Make Rapid Progress Despite Challenges

Tony Hagen @oncobiz
Published: Tuesday, Nov 18, 2014
Dr. Marcela V. Maus

Marcela V. Maus, MD, PhD

When Marcela V. Maus, MD, PhD, thinks of the challenge of bringing chimeric antigen receptor (CAR) therapies to market in the battle against cancer, she is reminded of the auto industry’s first days.

American industrialists managed to streamline the process of making autos from one at a time to several rolling off the assembly line every minute, and the same kind of revolution could make CARs available on a broad scale, said Maus.

“Right now we’re at the very beginning, and I think this has tremendous potential to become something that can be manufactured by different groups in different plants all over the world,” Maus, director of Translational Medicine and Early Clinical Development at the Abramson Cancer Center at the University of Pennsylvania in Philadelphia (UPenn), said in an interview.

The CAR technologies currently in development for hematologic cancers are a form of adoptive cell therapy in which the patient’s T cells are cultured and then primed to specifically recognize CD19, a protein expressed on normal and malignant cells of B-cell lineage. Thus, CD19 presents a suitable tumor-associated antigen against which to target anticancer agents (Figure).

The experimental technology has been successfully used to combat acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma, bringing many patients who participated in clinical trials into complete remission (Table). The success of these therapies has caused much excitement, and hopes are high that the CAR approach could one day become a frontline treatment for many types of cancer, including solid tumors such as breast, ovarian, and prostate cancers.

Getting CAR therapies to market will involve the crossing of many hurdles, according to researchers, pharmaceutical executives, and industry observers, particularly in light of the manufacturing complexity and safety concerns involved. The drug industry, however, is more than willing to tackle the task of translating CAR therapies to clinical practice.

Figure. Chimeric antigen receptor (CAR) technology

Chimeric antigen receptor (CAR) technology

Illustration courtesy of Novartis Pharmaceuticals

“It’s not without challenges,” said Usman Azam, MD, global head of the Cell and Gene Therapies Unit at Novartis Pharmaceuticals, which is working with UPenn to bring the CAR therapy CTL019 through clinical trials. “This is new for the agencies, it’s new for the hospital systems, it’s new for Novartis, but I think we have the building blocks in place. We have incredibly compelling data, and we’re going to be sharing some insights and a lot more at the upcoming ASH [American Society of Hematology] meeting. The data are showing great outcomes out to three years in the ALL population.”

Azam said his company is “doubling down” on immunotherapy, including CTL019, for which the FDA has granted breakthrough therapy status, allowing Novartis steady guidance throughout the clinical trials process to aid in bringing what could be a critical new agent to market as rapidly as possible.

Trials of CAR therapies by different industry/ academic partnerships have been conducted among pediatric and adult patients with relapsed or refractory leukemia, often resulting in complete remission lasting upward of a year or longer. The success for patients whose cancers were resistant to multiple other treatments has spurred huge investment to bring this technology out of the laboratory and into commercialization, and to explore the breadth of ways in which this form of immunotherapy could be employed.

Novartis Buys Former Provenge Plant

Hoping to be the first to bring CAR therapy to market, Novartis in 2012 purchased the 173,100-sq-ft Morris Plains, New Jersey, plant that Dendreon had hoped would help make a financial success of sipuleucel-T (Provenge). The prostate cancer vaccine is similar to Novartis’ CTL019 in that both involve the removal of a patient’s T cells for modification at a manufacturing facility. In the $43 million acquisition, Novartis retained about 100 former Dendreon employees.

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