Abstract
The purpose of the present study was to evaluate the effectiveness of targeting Bruton's tyrosine kinase (BTK) with a specific BTK inhibitor, alpha-cyano-beta-hydroxy-beta-methyl-N-(2,5-dibromophenyl)-propenamide (LFM-A13), for prevention of acute fatal graft-versus-host disease (GVHD) in a murine model of allogeneic bone marrow transplantation (BMT). Vehicle-treated control C57BL/6 mice receiving bone marrow/splenocyte grafts from allogeneic BALB/c donors developed severe multi-organ acute GVHD and died after a median survival time (MST) of 40 d. LFM-A13 treatment (25 mg/kg/d) significantly prolonged the MST of the BMT recipients to 47 d. The probability of survival at 2 months after BMT was 2 +/- 2% for vehicle-treated control mice and 22 +/- 6% for mice treated with LFM-A13 (P = 0.0008). Notably, the combination regimen of LFM-A13 plus the standard anti-GVHD drug methotrexate (MTX) (10 mg/m(2)/d) was more effective than LFM-A13 alone, while the combination regimen of LFM-A13 plus the novel anti-GVHD drug JANEX-1 (60 mg/kg/d), targeting Janus kinase 3, was more effective than LFM-A13, JANEX-1 or MTX alone. More than 70% of recipients receiving this most effective GVHD prophylaxis (LFM-A13 + JANEX-1) remained alive throughout ...Continue Reading
References
Apr 1, 1988·Transplantation·G HaleH Waldmann
Mar 10, 1995·Science·H Steller
Apr 1, 1994·Immunological Reviews·D J Rawlings, O N Witte
Aug 1, 1995·Teratology·J SutoK Fukuta
Jan 1, 1996·Cancer Investigation·R J BerensonM S Krieger
Apr 1, 1997·Bone Marrow Transplantation·J S BrysonA M Kaplan
Jan 1, 1998·Transplantation Proceedings·R J Stratta
Sep 29, 1998·Biochemical Pharmacology·F M Uckun
Jan 9, 1999·The Journal of Biological Chemistry·A VassilevF M Uckun
Mar 27, 1999·The Journal of Biological Chemistry·S MahajanF M Uckun
Aug 14, 1999·Immunology·H KandaY Nojima
Jan 6, 2000·Transfusion Science·O IlhanH Koç
Mar 22, 2000·Acta Haematologica·J TanakaM Imamura
Apr 27, 2000·Current Opinion in Immunology·T Kurosaki
Aug 25, 2001·Blood·M Cetkovic-CvrljeF M Uckun
Mar 9, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sangita MukhopadhyayBalachandran Ravindran
Mar 16, 2002·Science·Jia-Wang WangWilliam G Kerr
May 16, 2002·Blood·Fatih M UckunMarina Cetkovic-Cvrlje
Oct 23, 2002·Leukemia & Lymphoma·Marina Cetkovic-CvrljeFatih M Uckun
Jun 18, 2003·The Journal of Experimental Medicine·Nicole J HorwoodBrian M J Foxwell
Oct 22, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Arun R RaoSeema S Ahuja
Nov 8, 2003·International Journal of Hematology·James L M FerraraTakanori Teshima
Jun 8, 2004·Current Pharmaceutical Design·M Cetkovic-Cvrlje, H E Tibbles
Citations
Jun 26, 2012·Cellular & Molecular Immunology·Marina Cetkovic-CvrljeKetaki Ghate
Mar 16, 2013·OncoTargets and Therapy·Osmond J D'Cruz, Fatih M Uckun
Feb 27, 2008·International Reviews of Immunology·Fatih M Uckun
Feb 28, 2015·Journal of Immunotoxicology·Marina Cetkovic-CvrljeHwee Kiat Gong
Jun 17, 2008·Expert Opinion on Therapeutic Targets·Laura L RokoszMaria L Webb
Sep 14, 2010·Expert Opinion on Therapeutic Patents·Fatih M Uckun, Sanjive Qazi
May 23, 2012·Expert Opinion on Investigational Drugs·Tadeusz Robak, Ewa Robak
Feb 24, 2016·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Takanori TeshimaRobert Zeiser
Feb 24, 2016·Human Immunology·Petya Apostolova, Robert Zeiser
Oct 11, 2015·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Takanori TeshimaRobert Zeiser
Feb 13, 2016·Expert Review of Clinical Immunology·Leslie J CroffordPeggy L Kendall
Jul 17, 2007·American Journal of Reproductive Immunology : AJRI·Osmond J D'Cruz, Fatih M Uckun
May 16, 2013·Scandinavian Journal of Immunology·L VargasC I E Smith
Nov 17, 2009·British Journal of Haematology·Fatih M UckunChen Mao
Jan 11, 2013·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Kelli P MacDonaldPavan Reddy
Nov 14, 2013·PloS One·Tiantian ZhangXiaohua Mao
Jul 5, 2013·PLoS Pathogens·Karin StrijbisHidde L Ploegh
Sep 8, 2016·Journal of Immunotoxicology·Jordan KuiperMarina Cetkovic-Cvrlje
Jul 15, 2017·Journal of Immunotoxicology·Marina Cetkovic-CvrljeKylie A Bruner
Feb 29, 2020·Expert Opinion on Therapeutic Targets·Kazim SahinFatih M Uckun
May 10, 2021·International Immunopharmacology·Amir Hossein MansourabadiAliakbar Amirzargar