HOUSTON – Neutralizing granulocyte-macrophage colony-stimulating factor (GM-CSF) may be an effective strategy not only to manage toxicities associated with chimeric antigen receptor (CAR) T-cell therapy, but also to enhance CAR-T cell function, an investigator reported at the Transplantation & Cellular Therapy Meetings.
The GM-CSF targeted monoclonal antibody lenzilumab reduced neurotoxicity and cytokine release syndrome (CRS) related to CD19-targeted CAR T-cell therapy in a patient-derived xenograft model, said investigator Rosalie M. Sterner, an MD-PhD student in the department of immunology at Mayo Clinic, Rochester, Minn.
Other investigations showed that neutralizing or knocking out GM-CSF enhanced the antitumor functions of the CAR T cells, Ms. Sterner said in a podiumat the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research. At its meeting, the American Society for Blood and Marrow Transplantation announced a new name for the society: American Society for Transplantation and Cellular Therapy (ASTCT).
“GM-CSF blockade does not impair CAR T-cell effector function, and in fact, enhances CAR T-cell effector functions in certain models, and actually can help to ameliorate CAR T-cell associated toxicities,” Ms. Sterner said.
Based on these early findings, the investigators have designed a phase 2 clinical trial to see if lenzilumab can prevent CAR T cell-related toxicities in patients with diffuse large B-cell lymphoma.