CAR-T therapy CART4-34 destroys cancer cells in mice without suppressing immunity

Researchers report that CART4-34, a CAR-T therapy targeting the IGHV4-34 receptor, eliminated B‑cell cancer cells in mice while sparing healthy B cells, and the developers say a phase I trial is being planned.

Researchers report a new CAR-T therapy, called CART4-34, that targets B‑cell receptors carrying the IGHV4-34 gene. In mice engineered to model diffuse large B‑cell lymphoma, CART4-34 destroyed cancer cells as effectively as conventional CD19 CAR-T therapy while sparing healthy non-cancerous B cells. Antibodies to IGHV4-34 are reported as common in some people with lupus, and the team tested patient cells in laboratory experiments. The developers say they are planning a phase I trial for cancer or an autoimmune disease. Key findings: - CART4-34 is engineered to target B‑cell receptors carrying the IGHV4-34 gene. - In genetically modified mice with diffuse large B‑cell lymphoma, CART4-34 matched CD19 CAR-T in killing cancer cells. - CART4-34 spared healthy non-cancerous B cells, whereas CD19 CAR-T destroys all CD19-bearing B cells and can lead to immune suppression. - Lab tests using cells from people with lupus showed CART4-34 selectively removed IGHV4-34–bearing cells and the corresponding antibodies. - The researchers say they are planning a phase I clinical trial for cancer or an autoimmune condition. - The article reports that up to 60% of lymphomas may have B cells that carry IGHV4-34. Summary: The reported results indicate CART4-34 can selectively remove cancerous B cells in mice without broad depletion of healthy B cells, which is a known limitation of CD19-targeting CAR-T. It is not yet known how many patients would benefit, because the targeted receptor is not present in all lymphomas or autoimmune cases. A phase I trial has been announced and further testing in people will determine whether the approach translates to clinical care.