A Potent Glioma Targeting CAR T-Cell With Minimal Off-Target Toxicity

SUMMARY

• IL13Ra2 is a cancer testis antigen that is expressed in 50-80% of glioblastoma cells, has no basal expression in the healthy tissue, and is correlated with poor patient prognosis. Problematically, all attempts to target this antigen therapeutically have been with IL13-mutant CAR-T cells that have significant off-target binding to closely related and ubiquitously expressed IL13Ra1.
• Using hybridoma technology, the inventors isolated an antibody that selectively binds to IL13Ra2 and has no off-target interactions with closely related ILRa1 as verified by cell binding experiments. Thus, the antibody is amenable for use in a wide variety of glioblastoma immunotherapy modalities when expressed as an scFv.
• The invention is an anti-IL13Ra2 chimeric antigen receptor (CAR) T cell. The invention CAR T cells can potently and selectively target glioblastoma tumors with low risk of off-target toxicity, thus offering significant improvements over previous generations of anti-IL13Ra2 immunotherapy. 
• In a mouse glioma xenograft model, the investigators demonstrated the capability of their anti-IL13Ra2 CAR T cells to extend mouse survival time in a statistically significant fashion. Moreover, the CAR-T cells were shown to have no off-target binding to IL13Ra1 as measured during in vitro cell binding experiments.  

FIGURE

ADVANTAGES

ADVANTAGES

• Highly selective binding to IL13Ra2
• No interactions with closely related IL13Ra1 
• Antagonistic to IL13 ligand binding

APPLICATIONS

• Cancer immunotherapy (glioblastoma)
• Research tools

PUBLICATIONS

• Krenciute, G; et al. Characterization and functional analysis of scFv-based chimeric antigen receptors to redirect T Cells to IL13Ra2-positive Glioma. Mol Ther. 2016 Feb; 24(2): 354-363.
• Pituch, KC; et al. Adoptive transfer of IL13Ra2-specific chimeric antigen receptor T cells creates a pro-inflammatory environment in glioblastoma. Mol Ther. 2018 Apr 4;26(4): 986-995.