08.09.22

Enhanced AC133-Specific CAR T Cell Therapy Induces Durable Remissions in Mice with Metastatic Small Cell Lung Cancer

Taromi S, Firat E, Simonis A, et al. Enhanced AC133-Specific CAR T Cell Therapy Induces Durable Remissions in Mice with Metastatic Small Cell Lung Cancer. Cancer Letters. 2022; 538 (doi: 10.1016/j.canlet.2022.215697). By combining three different kinds of immunotherapy, researchers say they achieved long-lasting remission in mice with metastatic small cell lung cancer (SCLC). This incurable disease normally responds to chemotherapy for a short period before treatment-selected tumor stem cells expressing the AC133 epitope of the CD133 stem cell marker trigger relapse. In a humanized orthotopic SCLC model, the introduction of AC133-specific chimeric antigen receptor (CAR) T cells following chemotherapy induced clinical benefits — including eliminating cancer stem cells and increasing survival — but failed to completely eradicate tumors. Investigators responded by adding an anti-programmed death-ligand 1 (PD-L1) antibody and CD73-inhibitor to the CAR T cell regimen as a way to counter the immune-escape mechanisms mediated by PD-L1 and CD73 expression. The triple-immunotherapy approach specifically eliminates chemotherapy-resistant tumor stem cells, curing 25% of the lab animals tested without inducing graft-versus-host disease or bone marrow failure.
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