CNS CANCER: Preclinical studies have identified CD133-targeted CAR T cells as a potential therapeutic approach in glioblastoma multiforme (GBM)

Kevin Sovet

June 17, 2020

SCIENTIFIC

CNS CANCER

Preclinical studies have identified CD133-targeted CAR T cells as a potential therapeutic approach in glioblastoma multiforme (GBM). This is being moved into the clinic by Empirica Therapeutics.

 

The Rational Development of CD133-Targeting Immunotherapies for Glioblastoma

DOI: https://doi.org/10.1016/j.stem.2020.04.008

HIGHLIGHTS

• Three immunotherapeutic modalities were developed to target CD133+ cells
• Anti-CD133 DATEs and CAR-T cells are active in patient-derived glioblastoma (GBM) models
• CD133-specific CAR-T (CART133) has enhanced activity in orthotopic GBM xenograft models
• Intra-tumoral CART133 does not induce acute systemic toxicity in humanized mouse models

 

Summary

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.

 

more info: https://www.sciencedirect.com/science/article/abs/pii/S1934590920301478