Russell W. Jenkins, MD, PhD, a physician investigator in the Krantz Family Center for Cancer Research at the Mass General Cancer Center and an assistant professor of Medicine at Harvard Medical School, is senior author of a new study in Cancer Immunology Research, “TBK1 is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids”.
The study was a collaboration with the late Soldano Ferrone, MD, PhD, and was carried across the finish line by his daughter Cristina Ferrone, MD, Moshe Sade-Feldman, PhD, and several other collaborators at Massachusetts General Hospital.
What question were you investigating with this study?
What factors contribute to treatment resistance in chimeric antigen receptor (CAR)-T cell therapy treatments for solid tumors?
While CAR-T therapy treatments have proven effective in patients with blood tumors, their effectiveness in solid tumors has been limited due to a variety of factors, including the tumor microenvironment.
We used a unique 3D microfluidic model of tumors to investigate the mechanisms of treatment resistance to CAR-T cells that were designed to target B7-H3, a common antigen in solid tumor cancers.
What was unique about your approach?
While there are several different 3D models of tumors are available, they are limited in their ability to faithfully reproduce key elements of the tumor microenvironment.
We used patient-derived organotypic tumor spheroids (PDOTS), microphysiologic 3D models that replicate key features of the tumor microenvironment, enabling the study of interactions between tumors and immune cells.
What did you find?
We found