A cellular platform to enable targeted brain delivery of T cells to glioblastoma.

2053Background: Poor T cell homing hinders the development of effective cell therapy for central nervous system (CNS) malignancies. Lessons learnt from inflammatory brain diseases can give insight into how to overcome the blood brain barrier (BBB) blockade created by cancer. Activated Leukocyte Cell Adhesion Molecule (ALCAM; CD166) is a pathological adhesion molecule upregulated in the endothelium of a number of inflammatory/infiltrative CNS diseases, such as multiple sclerosis. Antibodies blocking ALCAM decrease leukocyte access to the brain and are currently being tested in a clinical trial for MS. Methods: We studied the difference in the dynamic signature of adhesion molecules in the “anergic” brain tumor endothelium and that of infiltrative brain conditions. Consequently, we mapped the ALCAM minimal binding region to domain 3 (D3) of CD6 and created an artificial molecule with the intent of creating a novel cellular platform to reverse endothelial anergy, through ALCAM specific binding. Results: GBM ...