ABSTRACT
Chimeric antigen receptor (CAR) T cells are an effective treatment for some blood cancers. However, the lack of tumor-specific surface antigens limits their wider use. We identified a set of surface antigens that are limited in their expression to cancer and the central nervous system (CNS). We developed CAR T cells against one of these antigens, LINGO1, which is widely expressed in Ewing sarcoma (ES). To prevent CNS targeting, we engineered LINGO1 CAR T cells lacking integrin ⍺4 (A4ko), an adhesion molecule essential for migration across the blood-brain barrier. A4ko LINGO1 CAR T cells were efficiently excluded from the CNS but retained efficacy against ES. We show that altering adhesion behavior expands the set of surface antigens targetable by CAR T cells.
One sentence summary Altering integrin-mediated adhesion provides tumor selectivity to CAR T cells by preventing homing to defined normal tissues but retaining tumor trafficking and anti-tumor activity.
Competing Interest Statement
EAM, DA, and TL are inventors on U.S. patent application 63/285843 describing the use of LINGO1 CAR T cells and knockout of integrin ⍺4 for the treatment of ES. The other authors are not declaring any conflicts of interest.
