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  • The Rational Development of CD133-Targeting Immunotherapies for Glioblastoma.

The Rational Development of CD133-Targeting Immunotherapies for Glioblastoma.

Cell stem cell (2020-05-29)
Parvez Vora, Chitra Venugopal, Sabra Khalid Salim, Nazanin Tatari, David Bakhshinyan, Mohini Singh, Mathieu Seyfrid, Deepak Upreti, Stefan Rentas, Nicholas Wong, Rashida Williams, Maleeha Ahmad Qazi, Chirayu Chokshi, Avrilynn Ding, Minomi Subapanditha, Neil Savage, Sujeivan Mahendram, Emily Ford, Ashley Ann Adile, Dillon McKenna, Nicole McFarlane, Vince Huynh, Ryan Gavin Wylie, James Pan, Jonathan Bramson, Kristin Hope, Jason Moffat, Sheila Singh
ABSTRACT

CD133 marks self-renewing cancer stem cells (CSCs) in a variety of solid tumors, and CD133+ tumor-initiating cells are known markers of chemo- and radio-resistance in multiple aggressive cancers, including glioblastoma (GBM), that may drive intra-tumoral heterogeneity. Here, we report three immunotherapeutic modalities based on a human anti-CD133 antibody fragment that targets a unique epitope present in glycosylated and non-glycosylated CD133 and studied their effects on targeting CD133+ cells in patient-derived models of GBM. We generated an immunoglobulin G (IgG) (RW03-IgG), a dual-antigen T cell engager (DATE), and a CD133-specific chimeric antigen receptor T cell (CAR-T): CART133. All three showed activity against patient-derived CD133+ GBM cells, and CART133 cells demonstrated superior efficacy in patient-derived GBM xenograft models without causing adverse effects on normal CD133+ hematopoietic stem cells in humanized CD34+ mice. Thus, CART133 cells may be a therapeutically tractable strategy to target CD133+ CSCs in human GBM or other treatment-resistant primary cancers.

MATERIALS
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Brand
Product Description

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