A new method of using CAR-T therapy to fight B-cell lymphomas has been developed by doctors at University Hospitals Seidman Cancer Center and Case Western Reserve University. This innovative therapy triples the amount of antigens that the CAR T-cells can target and destroy, bypassing one of the stickiest problems in dealing with B-cell cancers. Since B-cells are part of the immune system, it can be tricky to overcome them with the use of traditional CAR-T therapy.
Chimeric antigen receptor T-cell therapy, or CAR-T therapy for short, is a treatment that first involves removing T-cells from a cancer patient. Though a time-consuming process, the T-cells are genetically altered before being injected back into the patient’s body. The CAR T-cells, after being modified, have been turned into immune cells that hunt and destroy cancer cells based on certain receptors.
This has been one of the challenges of treating B-cell lymphomas with CAR-T therapy. Previous treatments for B-cell cancer used chimeric cells to attack the CD19 receptor — but only that receptor. B-cells recognize this attack and have the ability to shed CD19, moving from CD19-positive to CD19-negative. It’s still an active cancer cell when this happens, but the CAR T-cells no longer recognize it as such with the missing receptor.
B-cells have additional receptors, and researchers are working on a product that will recognize and attack the BAFF-R, BCMA and TACI receptors. With a three-in-one approach like this, they think the B-cells won’t be able to elude immune system attacks from the CAR-T therapy. The new type of therapy is called B-cell Activating Factor, or BAFF. Its use will allow a CAR-T treatment to target not only CD19, but also additional types of cancers such as lymphomas.
All B-cell cancers have at least two of the receptors listed above, and some have all three. Study results published in Nature Communications showed that BAFF CAR-T was successful at destroying multiple different kinds of B-cell cancers. These include mantle cell lymphoma, acute lymphoblastic leukemia and multiple myeloma.
The researchers are filing an Investigational New Drug application with the Food & Drug Administration (FDA), along with Luminary Therapeutics. A clinical BAFF CAR-T therapy trial will be launched in 2022 for patients with non-Hodgkin lymphoma, which is one of the most common types of B-cell cancer.
Case Western and UH Seidman researchers jointly operate the Cellular Therapy Lab where the new work on BAFF CAR-T cells is being done. The Cellular Therapy Lab is a cutting edge facility where CAR T-cells can be manufactured faster and more cost effectively than in a traditional cellular lab.
Another benefit of BAFF CAR-T therapy that doctors have identified is that it spares newly developed B-cells that have not yet developed any of the target receptors. Previous CAR-T treatments could not distinguish between early and mature B-cells that express the CD19 marker. The specificity of BAFF CAR-T allows the patient’s immune system to stay in better shape during treatment, because early B-cells can replenish mature B-cells that are lost during treatment. This should, in turn, produce fewer side effects in patients undergoing treatment.