The Rational Development of CD133-Targeting Immunotherapies for Glioblastoma.

AC133 Antigen Animals Brain Neoplasms / therapy Glioblastoma / therapy Humans Immunotherapy Mice Neoplastic Stem Cells
CD133 GBM IgG chimeric antigen receptor T cells dual-antigen T cell engagers glioblastoma humanized mice immunotherapy

Journal

Cell stem cell
ISSN: 1875-9777
Titre abrégé: Cell Stem Cell
Pays: United States
ID NLM: 101311472

Informations de publication

Date de publication:
04 06 2020
Historique:
received: 28 03 2019
revised: 16 12 2019
accepted: 14 04 2020
pubmed: 29 5 2020
medline: 28 4 2021
entrez: 29 5 2020
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.stem.2020.04.008 PMID: 32464096
pubmed: 32464096
pii: S1934-5909(20)30147-8
doi: 10.1016/j.stem.2020.04.008
pii:
doi:

Substances chimiques

AC133 Antigen 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

832-844.e6

Subventions

Organisme : CIHR
Pays : Canada

Informations de copyright

Copyright © 2020 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests P.V., C.V., R.W., J.M., and S.S. have patents around CD133 binding agents and uses thereof. These patents include Canadian Patent Application no. 2,962,157; Chinese Patent Application no. 2017800782373; European Patent Application no. EP17863201; Japanese Patent Application no. 2019-521046; and U.S. Patent Application no. 16/342,807. P.V., C.V., J.M., and S.S. are also shareholders of Empirica Therapeutics, which has an exclusive license to the IP as mentioned above. P.V. and D.B. are employees of Empirica Therapeutics.

Auteurs

Parvez Vora (P)

McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada; Surgery, Faculty of Health Sciences, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada.

Chitra Venugopal (C)

McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada; Surgery, Faculty of Health Sciences, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada.

Sabra Khalid Salim (SK)

McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada; Departments of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada.

Nazanin Tatari (N)

McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada; Departments of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada.

David Bakhshinyan (D)

McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada; Departments of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada.

Mohini Singh (M)

McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada; Departments of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada.

Mathieu Seyfrid (M)

McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada; Surgery, Faculty of Health Sciences, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada.

Deepak Upreti (D)

McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada; Surgery, Faculty of Health Sciences, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada.

Stefan Rentas (S)

McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada; Departments of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada.

Nicholas Wong (N)

McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada.

Rashida Williams (R)

Donnelly Centre, Department of Molecular Genetics, Institute of Biomolecular Engineering, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada.

Maleeha Ahmad Qazi (MA)

McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada; Departments of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada.

Chirayu Chokshi (C)

McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada; Departments of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada.

Avrilynn Ding (A)

McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada.

Minomi Subapanditha (M)

McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada.

Neil Savage (N)

McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada; Departments of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada.

Sujeivan Mahendram (S)

McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada; Surgery, Faculty of Health Sciences, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada.

Emily Ford (E)

McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada.

Ashley Ann Adile (AA)

McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada; Departments of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada.

Dillon McKenna (D)

McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada; Surgery, Faculty of Health Sciences, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada.

Nicole McFarlane (N)

McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada.

Vince Huynh (V)

Department of Chemistry and Chemical Biology, McMaster University, Hamilton ON L8S 4M1, Canada.

Ryan Gavin Wylie (RG)

Department of Chemistry and Chemical Biology, McMaster University, Hamilton ON L8S 4M1, Canada.

James Pan (J)

Donnelly Centre, Department of Molecular Genetics, Institute of Biomolecular Engineering, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada.

Jonathan Bramson (J)

Department of Pathology and Molecular Medicine, McMaster University, 1280 Main St W, Hamilton, ON L8S 4L8, Canada.

Kristin Hope (K)

McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada.

Jason Moffat (J)

Donnelly Centre, Department of Molecular Genetics, Institute of Biomolecular Engineering, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada. Electronic address: j.moffat@utoronto.ca.

Sheila Singh (S)

McMaster Stem Cell and Cancer Research Institute, McMaster University, Hamilton, ON, L8S 4K1, Canada; Departments of Biochemistry and Biomedical Sciences, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada; Surgery, Faculty of Health Sciences, McMaster University, 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada. Electronic address: ssingh@mcmaster.ca.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Glycoprotéines membranaires › Antigène AC133 › The Rational Development of CD133-Targeting...
questionsmedicales.fr › Eucaryotes › Animaux › The Rational Development of CD133-Targeting...
questionsmedicales.fr › Maladies du système nerveux › Tumeurs du système nerveux › Tumeurs du système nerveux central › Tumeurs du cerveau › The Rational Development of CD133-Targeting...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroépitheliales › Gliome › Astrocytome › Glioblastome › The Rational Development of CD133-Targeting...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › The Rational Development of CD133-Targeting...
questionsmedicales.fr › Thérapeutique › Biothérapie › Immunothérapie › The Rational Development of CD133-Targeting...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › The Rational Development of CD133-Targeting...
questionsmedicales.fr › Cellules › Cellules souches › Cellules souches tumorales › The Rational Development of CD133-Targeting...