The JAK3 inhibitor CP-690550 selectively reduces NK and CD8+ cell numbers in cynomolgus monkey blood following chronic oral dosing

Journal of Leukocyte Biology
Maryrose ConklynElizabeth Kudlacz

Abstract

Janus kinase 3 (JAK3) is a cytoplasmic tyrosine kinase associated with the common gamma chain, an integral component of cytokine receptors of the interleukin (IL)-2 family, including IL-4, -7, -9, -15, and -21. CP-690550 is a JAK3 inhibitor with immunosuppressive properties under development for transplantation. We evaluated alterations in circulating lymphocyte subsets in cynomolgus monkey blood following chronic (3-week), oral CP-690550 administration. Natural killer (NK) and CD8+ T cell numbers were reduced in a dose- and time-dependent manner; the latter was a primary effect on memory subsets. CD4+ T and B cell numbers were unaffected or slightly increased, respectively. NK cell numbers were reduced approximately 80% (vs. 35% in vehicle-treated animals) and returned to baseline levels within 3 weeks following treatment cessation. CD8+ T cells declined by a maximum 43% (vs. 25% for vehicle-treated animals) but rebounded significantly (300%) within 2 weeks after the last dose. Although CP-690550 did not result in reduction of CD4+ T cell number, these cells also increased (225%) within 2 weeks of treatment cessation. IL-15 is important for maintaining homeostasis of these cell types, and CP-690550 inhibited IL-15-induced CD69...Continue Reading

References

Nov 3, 1995·Science·T NosakaJ N Ihle
Apr 1, 1995·The Journal of Experimental Medicine·U von Freeden-JeffryR Murray
Nov 1, 1994·The Journal of Experimental Medicine·J J PeschonB L Davison
Apr 1, 1994·The Journal of Experimental Medicine·D F Tough, J Sprent
Oct 1, 1995·Current Opinion in Immunology·L L Lanier
Mar 1, 1997·The Journal of Clinical Investigation·W E CarsonM A Caligiuri
Mar 8, 2000·The Journal of Experimental Medicine·A MaJ P Lodolce
Mar 8, 2000·The Journal of Experimental Medicine·M K KennedyJ J Peschon
May 16, 2000·The Journal of Allergy and Clinical Immunology·W J Leonard, J X Lin
Jul 12, 2001·Proceedings of the National Academy of Sciences of the United States of America·J T TanC D Surh
Dec 26, 2001·Transplantation Proceedings·R A Kirken
Dec 26, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christine J PitcherLouis J Picker
Feb 15, 2003·Blood·Thomas RansonJames P Di Santo
May 8, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marion BerardDavid F Tough
Nov 1, 2003·Science·Paul S ChangelianDominic C Borie
Nov 18, 2003·Immunological Reviews·Anna Valujskikh, Fadi G Lakkis
Dec 18, 2003·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Elizabeth KudlaczPaul Changelian

❮ Previous
Next ❯

Citations

Jun 8, 2013·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Yasuko Furumoto, Massimo Gadina
Feb 4, 2010·Nature Reviews. Nephrology·Antoine DurrbachBernard Charpentier
Feb 20, 2013·Nature Reviews. Rheumatology·John J O'SheaIain B McInnes
Nov 20, 2009·The Journal of Biological Chemistry·Frank ErdmannGunter Fischer
Jun 12, 2012·The Journal of Clinical Investigation·Roberto BellucciJerome Ritz
Feb 1, 2008·Arthritis Research & Therapy·Anthony J MiliciPaul Changelian
Jan 15, 2014·PloS One·Elisa PiscianzAlberto Tommasini
Feb 27, 2008·International Reviews of Immunology·Jonghwa Won, Ge Hyeong Lee
Oct 3, 2007·Expert Opinion on Therapeutic Targets·Thomas Meyer, Uwe Vinkemeier
Jul 16, 2013·Transplantation Reviews·Martin S Zand
Jul 24, 2012·Current Opinion in Pharmacology·Apostolos KontziasJohn J O'Shea
Mar 14, 2009·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·C John SperatiW H Linda Kao
Apr 24, 2015·Clinical and Experimental Immunology·C MeyerI Messaoudi
Nov 12, 2013·The Journal of Investigative Dermatology·Naoko OkiyamaStephen I Katz
Dec 15, 2015·Arthritis Research & Therapy·Alba Llop-GuevaraJuan Román
Mar 19, 2008·Biochemical and Biophysical Research Communications·Xiaonan ZhangZhenghong Yuan
Feb 5, 2008·European Journal of Pharmacology·Elizabeth KudlaczPaul Changelian
Mar 18, 2009·Immunological Reviews·Kamran GhoreschiJohn J O'Shea
Jul 17, 2007·American Journal of Reproductive Immunology : AJRI·Osmond J D'Cruz, Fatih M Uckun
Jun 19, 2008·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·E van GurpG Chan
Jan 30, 2008·Transplant International : Official Journal of the European Society for Organ Transplantation·Shivaprakash GangappaChristian P Larsen
Nov 4, 2006·Transplant International : Official Journal of the European Society for Organ Transplantation·Geraldine RousvoalDominic C Borie
Jul 16, 2010·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·V D K D SewgobindC C Baan
Jun 6, 2006·Biochemical Pharmacology·Claude HaanIris Behrmann
May 29, 2015·Transplantation·Thomas ReschKatja Kotsch
Jun 17, 2016·Journal of the European Academy of Dermatology and Venereology : JEADV·A K GuptaW Abramovits
Dec 2, 2011·Acta Biochimica Et Biophysica Sinica·Wei Wu, Xiao-Hong Sun
Nov 23, 2018·Science Translational Medicine·Hart S DenglerNico Ghilardi
Jul 24, 2020·Current Rheumatology Reports·Virginia Reddy, Stanley Cohen
Jul 20, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maren Q DeGottardiLouis J Picker
Jun 15, 2021·Frontiers in Pharmacology·Shahin ShamsJudith F Ashouri

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.

Related Papers

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
Elizabeth KudlaczPaul S Changelian
American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
Evelien A F J van GurpG Chan
© 2021 Meta ULC. All rights reserved