CAR-T Engager proteins optimize anti-CD19 CAR-T cell therapies for lymphoma

B cell lymphoma therapy has been transformed by CD19-targeting cellular therapeutics that induce high clinical response rates and impressive remissions in relapsed and refractory patients. However, approximately half of all patients who respond to CD19-directed cell therapy relapse, the majority within 6 months. One characteristic of relapse is loss or reduction of CD19 expression on malignant B cells. We designed a unique therapeutic to prevent and reverse relapses due to lost or reduced CD19 expression. This novel biologic, a CAR T Engager, binds CD20 and displays the CD19 extracellular domain. This approach increases the apparent CD19 antigen density on CD19-positive/CD20-positive lymphoma cells, and prevents antigen-loss induced relapse, as CD19 bound to CD20 remains present on the cell surface. We demonstrate that this novel therapeutic prevents and reverses lymphoma relapse in vitro and prevents CD19-negative lymphoma growth and relapse in vivo.

Automated summary

CD19-targeting cellular therapeutics have shown high clinical response rates in B cell lymphoma therapy, however, many patients relapse within 6 months. Researchers have designed a novel CAR T Engager that can prevent and reverse relapses caused by loss or reduction of CD19 expression. In vitro and in vivo studies have demonstrated its effectiveness in preventing lymphoma relapse.