Double CAR T immune therapy for relapsed B cell lymphoma

This initial study looked at using CAR T cells with two targets to treat relapsed B cell non-Hodgkin lymphoma (NHL). It found that this type of immunotherapy was safe and effective, and may cause less inflammation than other types of CAR T cell treatment.

Chimeric antigen receptor T (CAR T) cells are a treatment for cancers including relapsed B cell lymphomas. T cells are a type of white blood cell that is involved in destroying cancer cells. Cells have various molecules on their surfaces. Each T cell has receptors that can recognize a specific target molecule. The T cells will destroy any cells that have the target. CAR T treatment involves removing a patient’s own T cells and altering them to have receptors designed in the laboratory. Most of these designed receptors target CD19, which is a protein on B cells including B cell lymphoma.

CAR T cells release small molecules called cytokines that signal inflammation. In some patients, this causes cytokine release syndrome or inflammation throughout the body. This inflammation can also cause neurological side effects such as headaches, slurred speech, or tremors. Despite these side effects, CAR T is an effective treatment for relapsed NHL.

However, some patients will relapse after CAR T treatment. When CD19 is targeted, lymphoma cells can evolve over time to have fewer CD19 proteins on their surface. When this happens, the CAR T treatment will no longer be effective. One way to prevent this is to design receptors that can recognize two target molecules. Tandem CAR 7 (TanCAR7) can recognize both CD19 and CD20, two molecules that B lymphoma cells have. It is unclear whether TanCAR7 T cell treatment is safe and effective for patients with relapsed NHL.

This study was a Phase I/IIa trial, which is the first study to use TanCAR7 T cells in humans. It included 28 people with hard-to-treat NHL. All patients received TanCAR7 after chemotherapy to kill cancer cells (conditioning). Patients were followed up for an average of 19.1 months.

79% of patients who received TanCAR7 T cells responded to treatment. 71% had a complete response, meaning the cancer could no longer be detected. 64% of patients did not have their lymphoma progress after 12 months. Of the patients who had a complete response, 85% did not have the cancer progress after 12 months.

50% of patients had cytokine release syndrome, and 14% had a serious case of this syndrome. The most common serious side effects were low white blood cell counts (61%) and fever (36%).

This study found that TanCAR7 T cell treatment is safe and effective for patients with relapsed B-cell NHL. It also suggests that this treatment may have fewer side effects from inflammation than conventional CD19 CAR T cell treatment.

This was an early study. Larger studies are needed to confirm that TanCAR7 is effective.