Combating Relapse in CAR19 T Cell Therapy: The Role of a Novel CD19-Anti-CD20 Bridging Protein

The abstract discusses the development of a novel approach to address the issue of patient relapse in B cell malignancies treated with CD19-targeted CAR T cells (CAR19s). The relapse is often due to the loss of CD19 expression on the cancer cells, leading to a reported relapse rate of up to 50%. Traditional attempts to treat relapsed patients by targeting a second antigen, such as CD22, have had limited success and many patients are unable to endure further intensive treatment regimens.

The study introduces a technology that reactivates the existing CAR19 T cells in patients to target the relapsing tumor cells. A protein was engineered by fusing the CD19 extracellular domain with anti-CD20 and anti-albumin components to create a stable, long-lasting bridging protein. This protein was shown to be highly stable and capable of directing the cytotoxic activity of CAR19 T cells against CD19-negative/CD20-positive cells with high potency.

In vitro and in vivo experiments demonstrated that the bridging protein could activate CAR19 T cells to eliminate CD19-negative tumor cells that were previously undetectable to them. The protein was effective in controlling and eradicating tumors in both prevention and relapse settings in animal models. The study concludes that the CD19-anti-CD20 bridging protein is a promising candidate for treating relapses in patients who have undergone CAR19 therapy.

The authors note that a GMP production campaign is in progress and a first-in-human trial is planned for patients with CD19-negative malignancies who have relapsed after CAR19 treatment and still have detectable levels of CAR19 T cells. The disclosures indicate affiliations with Aleta Biotherapeutics for several authors involved in the study.