The life sciences industry has just scratched the surface in terms of chimeric antigen receptor (CAR) T-cell therapy’s potential, according to a session at the Novartis Breakthrough Science media event held on November 10.

CAR-T therapy, which has emerged as one of the most promising new treatments for multiple myeloma, certain lymphomas and B-cell acute lymphoblastic leukemia, has found growing use in recent years. The treatment, however, is often expensive.

Manufacturing of CAR-Ts continues to improve, however. And in recent years, researchers have made progress in enhancing the fitness of CAR-T cells so that they have more potential for proliferation and “hopefully, overall, better benefit and higher response rates,” said Jennifer Brogdon, executive director, head of cell therapy research, department of exploratory immuno-oncology at the Novartis Institutes for BioMedical Research.

Manufacturing breakthroughs have enabled the therapy to be used at lower doses than in the past. In addition, improved potency could potentially avoid some of the adverse effects associated with first-generation approaches.

According to the American Cancer Society, side effects broadly associated with CAR-T can include cytokine release syndrome, nervous system problems, allergic reactions and other problems.

The CAR-T field is still young. In 2017, FDA approved Kymriah (tisagenlecleucel) from Novartis, the first gene therapy in the U.S. The FDA approval covers pediatric and young adult patients with B-cell precursor acute lymphoblastic leukemia that is refractory or in second or later relapse. The FDA also has indicated the drug for certain adults with relapsed or refractory large B-cell lymphoma.

At present, there are four FDA-approved CAR-Ts.

In addition to CAR-Ts, Brogdon is optimistic regarding the therapeutic potential of T cell receptors (TCRs), a protein complex present on the surface of T cells. Like CAR-Ts, TCRs are still based on using a patient’s immune cells that have been modified to attack cancer cells. “But unlike CAR-T, the TCRs can really zero in on proteins that are inside the cells,” Brogdon said. “You can think of mutant cancer proteins that are driving the disease that can be targeted in this fashion.”

There are several reasons Novartis thinks TCRs may be a better fit for solid tumors than CAR-Ts, Brogdon said. “One of those primary reasons is now we can go after tumor-specific antigens to minimize the risk of normal tissue toxicity,” she explained. “Hopefully, the ultimate goal is to find new antigens that are shared across different tumor types that could lead to broader therapies that might work across multiple cancers.”

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Filed Under: Oncology
Tagged With: CAR T-cell therapy, Kymriah, Novartis, T cell receptors, TCRs, tisagenlecleucel
 

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