A recent ACR Convergence presentation discussed the evolution and advances of CAR T cell therapies.
Both broad and specific approaches are being used in an attempt to develop the next generation of CAR T cell therapies.
Chimeric antigen receptor T (CAR T) cell therapies initially received FDA approval for use in B cell cancers, but have also been used in systemic lupus erythematosus, myositis and other B cell-related autoimmune diseases in recent times.
However, the benefits of CAR T therapies are offset by the fact that they are difficult to make, are expensive and are associated with severe side effects such as opportunistic infection and cytokine-related toxicities.
New research presented at the recent American College of Rheumatology Convergence in Washington detailed one expert’s attempts at making CAR T therapies safer, easier and more effective.
“Our overarching goal is to develop precision treatments that selectively eliminate the drivers of autoimmune damage while leaving the protective immune response intact,” said Associate Professor Maximillian Koning, from the Johns Hopkins University School of Medicine.
CAR T cells, which are normally autologous, are created by removing T cells and other white blood cells from patients and genetically altering them in a lab before infusing them into a patient.
“The modifications allow the patient’s T cells… to recognise desired antigens on the target cell surface and destroy them,” said the director of the Cellular Therapy Program for Autoimmune Diseases.
In an attempt to reduce the time and cost associated with genetically modifying a patient’s own cells, researchers are investigating the potential of making genetically modified T and natural killer (NK) cells from healthy donors. These donor cells could be produced ahead of time and stored for use when needed, similar to a blood transfusion.
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Another approach, according to Professor Koning, is the use of precision immunotherapies. Together with colleagues at Johns Hopkins, Professor Koning has developed chimeric autoantigen T cell receptor cells (CARCR T cells) for use in patients with antiphospholipid syndrome and other rheumatic diseases.
The CARCR T cells seek and destroy the self-reactive B cells involved in autoimmune disease processes while leaving healthy B cells untouched, which significantly minimises infection risk.
Professor Koning felt cellular and bispecific antibody therapies would have a substantial impact on the rheumatology field over the next decade.
“They will become commonplace and much less toxic, allowing them to be used beyond severe and refractory disease in the outpatient setting,” he said.
“[Consequently,] the costs of immune effector cell therapies should come down dramatically, and we will be able to combine the potential for longstanding remission with therapies that do not cause infection.”
