Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/100154
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: Different cytokine and stimulation conditions influence the expansion and immune phenotype of third-generation chimeric antigen receptor T cells specific for tumor antigen GD2
Author: Gargett, T.
Brown, M.
Citation: Cytotherapy, 2015; 17(4):487-495
Publisher: Elsevier
Issue Date: 2015
ISSN: 1465-3249
1477-2566
Statement of
Responsibility: 
Tessa Gargett and Michael P. Brown
Abstract: Background aims: Chimeric antigen receptor (CAR) T cells are a novel immunotherapy for cancer. To achieve anti-tumor efficacy, these cells must survive, expand, and persist after infusion into patients, functions that are reportedly best achieved by cells with a stem or central-memory rather than effector-memory phenotype. We have developed third-generation CAR T cells specific for the tumor-associated antigen GD2 for use in a phase I clinical trial. We investigated the optimal cell culture conditions for CAR T-cell production, and here we describe the relative effects of 3 activation and cytokine conditions on CAR T-cell expansion, effector function and phenotype. Methods: Peripheral blood mononuclear cells were activated by anti-CD3 and anti-CD28 or anti-CD3 and Retronectin. Activated cells were transduced with the CAR-encoding retroviral vector and expanded in either interleukin (IL)-2 or IL-7 and IL-15. Immune phenotype and expansion were tracked throughout the culture, and transduction efficiency, and subsequent GD2-specific effector functions were evaluated by flow cytometry and cytotoxic T lymphocytes assay. Results: CD3/Retronectin stimulation with IL-2 resulted in poorer activation, expansion and Th1 cytokine secretion of CAR T cells than CD3/CD28 stimulation with either IL-2 or IL-7 and IL-15. However, CAR T cells cultured in CD3/CD28/IL7/IL-15 and CD3/Retronectin/IL-2 had superior cytotoxic T lymphocyte activity and a more stem-like phenotype. Discussion: The combination of CD3 and CD28 with IL-7 and IL-15 gave the best balance of CAR T-cell expansion and potent GD2-specific effector functions while retaining a stem/memory phenotype, and these growth conditions will therefore be used to manufacture CAR T cells for our phase I clinical trial.
Keywords: Anti-CD3 and anti-CD28 stimulation; chimeric antigen receptor T cells; effector function; IL-7; IL-15; IL-2; immune phenotype; Retronectin
Rights: Crown Copyright © 2015 Published by Elsevier Inc. on behalf of International Society for Cellular Therapy. All rights reserved.
RMID: 0030023922
DOI: 10.1016/j.jcyt.2014.12.002
Grant ID: http://purl.org/au-research/grants/nhmrc/1010386
Appears in Collections:Medicine publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.