Dual Effects of Cyclooxygenase Inhibitors in Combination With CD19.CAR-T Cell Immunotherapy.

Frontiers in Immunology
Mingya YangAnita Schmitt

Abstract

Chimeric antigen receptor T (CAR-T) cells targeting CD19 came into clinical practice for the treatment of B cell lymphoma in 2018. However, patients being treated for B cell lymphoma often suffer from comorbidities such as chronic pain, cardiovascular diseases and arthritis. Thus, these patients frequently receive concomitant medications that include nonsteroidal anti-inflammatory drugs (NSAIDs) like cyclooxygenase (COX) inhibitors. Celecoxib, a selective COX-2 inhibitor, and aspirin, a non-selective COX-1 and COX-2 inhibitor, are being used as anti-inflammatory, analgesic and anti-pyretic drugs. In addition, several studies have also focused on the anti-neoplastic properties of COX-inhibitors. As the influence of COX-inhibitors on CD19.CAR-T cells is still unknown, we investigated the effect of celecoxib and aspirin on the quantity and quality of CD19.CAR-T cells at different concentrations with special regard to cytotoxicity, activation, cytokine release, proliferation and exhaustion. A significant effect on CAR-T cells could be observed for 0.1 mmol/L of celecoxib and for 4 mmol/L of aspirin. At these concentrations, we found that both COX-inhibitors could induce intrinsic apoptosis of CD19.CAR-T cells showing a significant ...Continue Reading

References

Apr 1, 1987·Journal of Clinical Pharmacology·R A KershawN Gerber
Feb 23, 1996·Journal of Chromatography. B, Biomedical Applications·F KeesH Grobecker
Jun 30, 2000·The New England Journal of Medicine·G SteinbachG Kelloff
Nov 9, 2001·The Journal of Biological Chemistry·Silvia Rossi PaccaniCosima T Baldari
Sep 2, 2003·Nature Reviews. Immunology·Bharat B Aggarwal
Jun 6, 2007·International Immunology·Michiel F van OosterwijkRené A W van Lier
Feb 23, 2008·Cellular and Molecular Life Sciences : CMLS·N R Jana
Nov 5, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Victor PeperzakJannie Borst
Jan 26, 2011·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Mario Roederer
Jul 9, 2011·Nature Immunology·E John Wherry
Jul 21, 2011·BMC Systems Biology·Pernille YdeAla Trusina
Mar 23, 2012·Immunological Reviews·Soumen BasakAlexander Hoffmann
Oct 16, 2014·The New England Journal of Medicine·Shannon L MaudeStephan A Grupp
Jul 18, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Cameron J TurtleDavid G Maloney
Aug 15, 2017·Molecular Therapy : the Journal of the American Society of Gene Therapy·James N KochenderferSteven A Rosenberg
Dec 12, 2017·The New England Journal of Medicine·Stephen J SchusterCarl H June
Dec 12, 2017·The New England Journal of Medicine·Sattva S NeelapuWilliam Y Go
Feb 1, 2018·The New England Journal of Medicine·Shannon L MaudeStephan A Grupp
Feb 1, 2018·The New England Journal of Medicine·Jae H ParkMichel Sadelain
Aug 4, 2018·Current Drug Targets·Natalia Tołoczko-IwaniukWojciech Miltyk
Aug 12, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Gunilla EnbladAngelica Loskog
Nov 23, 2018·Journal of Inflammation Research·Sivagami Giridharan, Mythily Srinivasan
Feb 10, 2019·Journal of Clinical Medicine·Susanne HofmannMichael Schmitt
Apr 24, 2019·Nature Biomedical Engineering·Louai LabaniehCrystal L Mackall
Jun 17, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Shuangshuang LiShuwen Yu

❮ Previous
Next ❯

Software Mentioned

GraphPad Prism
Open
Diva
FlowJo
SPSS

Related Concepts

Related Feeds

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis