A novel simplified method of generating cytomegalovirus-specific cytokine-induced killer cells of high specificity and superior potency with GMP compliance

A novel simplified method of generating cytomegalovirus-specific cytokine-induced killer cells of high specificity and superior potency with GMP compliance

Copyright © 2019 Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 205(2019) vom: 15. Aug., Seite 83-92
1. Verfasser: Luah, Yen Hoon (VerfasserIn)
Weitere Verfasser: Sundar Raj, Kirubavathy, Koh, Mickey B C, Linn, Yeh Ching
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2019
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Allogeneic hematopoietic stem cell transplant CD137 co-stimulation Cell therapy Cytokine-induced killer cells Cytomegalovirus IE1 protein, cytomegalovirus Immediate-Early Proteins Viral Matrix Proteins cytomegalovirus matrix protein 65kDa
Beschreibung
Zusammenfassung:Copyright © 2019 Elsevier Inc. All rights reserved.
We describe a method of rendering polyclonal cytokine-induced killer cells (CIK) specific against cytomegalovirus (CMV), focusing on GMP compliance. Peripheral blood mononuclear cells (PBMNC) are stimulated with pooled CMV peptides pp65 and IE-1 for 16-24 h and the reactive T cell subset which up-regulate CD137 is further co-stimulated with anti-CD137, followed by expansion in G-Rex flasks under standard CIK culture condition. This method generates a large number CMV-specific CIK with superior potency compared to published method currently in clinical trials. The cytotoxicity as measured by chromium release assay correlates with the upregulation of CD107a upon peptide re-challenge as measured by flow cytometry. CMV-CIK at maturity consist of mainly late effector memory CD8 T cells and have a skewed TCR repertoire with preferential expansion of a few families. Such CMV-CIK retain their function after freezing and thawing. CMV-CIK thus generated is ready for clinical trial against drug-resistant CMV disease
Beschreibung:Date Completed 20.04.2020
Date Revised 20.04.2020
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2019.06.007