1. The IAP antagonist birinapant enhances chimeric antigen receptor T cell therapy for glioblastoma by overcoming antigen heterogeneity
- Author
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Edward Z. Song, Xin Wang, Benjamin I. Philipson, Qian Zhang, Radhika Thokala, Logan Zhang, Charles-Antoine Assenmacher, Zev A. Binder, Guo-li Ming, Donald M. O’Rourke, Hongjun Song, and Michael C. Milone
- Subjects
Cancer Research ,Oncology ,Molecular Medicine ,Pharmacology (medical) - Abstract
Antigen heterogeneity that results in tumor antigenic escape is one of the major obstacles to successful chimeric antigen receptor (CAR) T cell therapies in solid tumors including glioblastoma multiforme (GBM). To address this issue and improve the efficacy of CAR T cell therapy for GBM, we developed an approach that combines CAR T cells with inhibitor of apoptosis protein (IAP) antagonists, a new class of small molecules that mediate the degradation of IAPs, to treat GBM. Here, we demonstrated that the IAP antagonist birinapant could sensitize GBM cell lines and patient-derived primary GBM organoids to apoptosis induced by CAR T cell-derived cytokines, such as tumor necrosis factor. Therefore, birinapant could enhance CAR T cell-mediated bystander death of antigen-negative GBM cells, thus preventing tumor antigenic escape in antigen-heterogeneous tumor models
- Published
- 2022
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