Dr Smith on Translating CAR T-Cell Therapies From Hematologic to Solid Malignancies

“Within solid tumors, there are a few more challenges [with CAR T-cell therapy] than we see with liquid tumors. For example, there are tumor suppressive environments. In other words, the T cells that are within and around the tumor and the other cells of the immune system actively suppress the immune system and make those T cells particularly less effective.”

Sonali M. Smith, MD, the chief of the Section of Hematology/Oncology and the holder of the Elwood V. Jensen Professorship of Medicine at the University of Chicago Medical Center (UChicago Medicine), discussed ongoing efforts to translate benefit with CAR T-cell therapy from hematologic malignancies to the solid tumor space.

CAR T-cell therapy has revolutionized the treatment of patients with hematologic malignancies, including non-Hodgkin lymphoma, multiple myeloma, and certain subtypes of leukemia, Smith began. The excitement that these therapies have generated in hematologic malignancies has spurred investigators to pursue this drug class in solid tumors, she continued.

However, treating patients with solid tumors with CAR T-cell therapy presents unique challenges compared with hematologic malignancies, including tumor suppressive environments and a lack of effective targets, Smith noted. Tumor-associated antigens such as CD20 and CD19 that can be targeted with CAR T-cell therapy in hematologic cancers because they are also expressed in normal human tissues, she added.

In recent years, research groups, including those at the University of Chicago, have been working to identify new targets for CAR T-cell therapy in solid tumors, Smith said. Targets that have been evaluated include PD-L1, PSMA, Claudin 18.2, and EGFR, she said. CAR T-cell therapies that are being designed for use in patients with solid tumors also require careful engineering, which has now become possible through recent technological advances, she added. Investigators at the David and Etta Jonas Center for Cellular Therapy of UChicago Medicine including Michael R. Bishop, MD, and Daniel Olsen, MD, are working to develop effective cellular therapies for the treatment of patients with solid tumors, she concluded.