Journal Article

Targeting Tumor Heterogeneity in Glioblastoma: Bispecific T Cells Exhibit Enhanced Effector Functions and Offset Antigen Loss Escape Variants

Ashoori, Aidin, Chow, Kevin KH, Heslop, Helen E, Gottschalk, Stephen, Salsman, Vita S, Yvon, Eric, Gerken, Claudia, Mukherjee, Malini, Ahmed, Nabil, Hegde, Meenakshi

2011

Overview

Chimeric Antigen Receptor (CAR)-redirected T cells have shown promising results in preclinical models and early clinical trials. The downregulation or mutation of targeted antigens is a common tactic used by cancer cells to create antigen loss escape variants; culminating in relapse. Targeting multiple antigens on tumor cells, simultaneously, could offset this escape mechanism and possibly result in enhanced CAR T cell activation. The pattern of heterogeneity in GBM favors near complete targeting of tumor subpopulations using multi-specific T cell approach. Pooled CAR T cells as well as bi-specific CAR T cells can effectively target antigen escape variant tumor cells, yet bispecific T cells exhibit significantly enhanced effector functions.