Novel Allogeneic CD19-Directed CAR T-Cell Agents for LBCL

Frederick Locke, MD, a medical oncologist and translational researcher in the Department of Blood and Marrow Transplant and Cellular Immunotherapy at Moffitt Cancer Center, explains the allogeneic CD19-directed chimeric antigen receptor (CAR) T-cell therapies, ALLO-501 and ALLO-501A, and how they work.

An investigation of ALLO-501A for the treatment of patients with large B-cell lymphoma is occurring in the phase 2 ALPHA2 study (NCT04416984), which aims to include 100 patients. Patients in the study will be treated with ALLO-501A in addition to ALLO-647 and lymphodepletion chemotherapy consisting of fludarabine and cyclophosphamide. The key end point being assessed is objective response rate (ORR).

ALLO-501A is an identical drug to ALLO-501, says Locke. The one difference between the agents is that ALLO-501A has no rituximab (Rituxan) kill switch. Both agents have a gene editing component, which allows for each agent to be used in combination with chemotherapy and a CD52-directed CAR T product, according to Locke.

Transcript:

0:08 | ALLO-501 and ALLO-501A are off-the-shelf allogeneic CD19-directed CAR T-cell therapies. The only difference between ALLO-501 and ALLO-501A is that ALLO-501A has removed a rituximab kill switch, which was present in ALLO-501. Otherwise, they're identical. These CAR T cells have gene editing. So, not only do they express the CD19 CAR, but their gene-edited. The track locus is removed so that the T cell receptor is not expressed and therefore, the cells are unlikely to cause graft-versus-host disease.

0:56 | The CAR T cells are gene-edited so that CD52, which is a cell surface protein that's on immune cells, is removed from the CAR T cells and that actually allows us to also give an antibody against CD52 as part of the conditioning chemotherapy regimen, which ALLO-647. It's a monoclonal antibody against CD52, which has been removed from those CAR T cells.