Faculty Collaboration Database

Restricting CAR T Cell Trafficking Expands Targetable Antigen Space. bioRxiv 2024 Feb 11

Date

02/19/2024

Pubmed ID

38370665

Pubmed Central ID

PMC10871312

DOI

10.1101/2024.02.08.579002

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 α₄ (A4^ko), an adhesion molecule essential for migration across the blood-brain barrier. A4^ko 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.

Author List

Morales EA, Dietze KA, Baker JM, Wang A, Avila SV, Iglesias F, Radhakrishnan SV, Mause EV, Olson ML, Sun W, Rosati E, Chidester SL, Iraguha T, Fan X, Atanackovic D, Luetkens T

Author

Sabarinath Venniyil Radhakrishnan MD Assistant Professor in the Medicine department at Medical College of Wisconsin