A humanized non-FcR-binding anti-CD3 antibody, visilizumab, for treatment of steroid-refractory acute graft-versus-host disease.

Blood
Paul A CarpenterClaudio Anasetti

Abstract

Visilizumab is a humanized anti-CD3 monoclonal antibody characterized by a mutated IgG2 isotype, lack of binding to Fcgamma-receptors, and ability to induce apoptosis selectively in activated T cells. To test pharmacokinetics, safety, and immunosuppressive activity of visilizumab, 17 patients with glucocorticoid-refractory acute graft-versus-host disease (GVHD) were enrolled in a phase 1 study. Six patients were given 7 doses of visilizumab (0.25 or 1.0 mg/m(2)) on days 1, 3, 5, 7, 9, 11, and 13. Because multiple doses of 1 mg/m(2) caused delayed visilizumab accumulation and prolonged lymphopenia, the next 11 patients received a single dose of 3.0 mg/m(2) on day 1. GVHD improved in all patients; 15 were evaluable through day 42. Multiple dosing resulted in 1 of 6 complete responses (CRs) and 5 partial responses (PRs), but all 6 patients died at a median of 87 days after starting visilizumab therapy. Single dosing resulted in 6 of 9 CRs, 3 PRs, and 7 of 11 patients surviving after 260 to 490 days (median, 359 days; P =.03). There were no allergic reactions and 3 grade 1 acute infusional toxicities. Plasma Epstein-Barr virus (EBV) DNA titers more than 1000 copies/mL and posttransplant lymphoproliferative disease (PTLD) developed ...Continue Reading

References

Dec 1, 1990·The Journal of Experimental Medicine·C AnasettiP J Martin
Aug 1, 1994·The Journal of Infectious Diseases·Y J GanJ W Sixbey
Mar 26, 1999·Journal of Biopharmaceutical Statistics·D Johns, J S Andersen
May 18, 1999·Cancer Genetics and Cytogenetics·K F Wong, J K Chan
Jun 18, 1999·Annals of the New York Academy of Sciences·R HandgretingerT Klingebiel
Sep 1, 1999·British Journal of Haematology·L TrentinA De Rossi
Feb 3, 2000·Journal of Clinical Microbiology·H G NiestersA D Osterhaus
Mar 9, 2000·Annals of Oncology : Official Journal of the European Society for Medical Oncology·N MilpiedV Leblond
May 2, 2000·Journal of Clinical Microbiology·D M ZerrL M Frenkel
Jul 14, 2000·Journal of Hematotherapy & Stem Cell Research·K G McCaulH G Klingemann
Aug 2, 2000·Journal of Virological Methods·M SchuttenH G Niesters
Nov 22, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·P A CarpenterC Anasetti
Jun 8, 2001·Clinical Transplantation·M RembergerO Ringdén
Aug 21, 2001·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·D M ZerrC Anasetti

❮ Previous
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Citations

Apr 3, 2008·Inflammatory Bowel Diseases·Miles Sparrow
Jun 2, 2006·Springer Seminars in Immunopathology·Reinhard Marks, Jürgen Finke
Sep 3, 2013·Journal of Pharmacokinetics and Pharmacodynamics·Yanguang CaoWilliam J Jusko
Aug 12, 2006·Current Treatment Options in Gastroenterology·Pieter C F Stokkers, Daniel W Hommes
Oct 20, 2009·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Simona Cernea, Kevan C Herold
Jul 24, 2008·Bone Marrow Transplantation·C MessinaUNKNOWN EBMT Paediatric Working Party
Sep 22, 2009·Bone Marrow Transplantation·J PidalaC Anasetti
Dec 8, 2009·Bone Marrow Transplantation·D HodaM A Kharfan-Dabaja
Jul 18, 2012·Nature Reviews. Clinical Oncology·Catherine M BollardHelen E Heslop
Jul 21, 2007·Nature Reviews. Immunology·Lucienne Chatenoud, Jeffrey A Bluestone
May 7, 2010·Hybridoma·Luis E HinojosaAlejandro López-Requena
Mar 12, 2004·Anti-cancer Drugs·Arjan A van de LoosdrechtGert J Ossenkoppele
Apr 4, 2006·Current Opinion in Rheumatology·Margrit WiesendangerBetty Diamond
Jul 8, 2005·Journal of Clinical Gastroenterology·Seymour Katz
Dec 18, 2004·Current Opinion in Hematology·Javier Bolaños-Meade, Georgia B Vogelsang
Oct 12, 2005·Journal of Pediatric Hematology/oncology·Markus G SeidelChristina Peters
Oct 9, 2009·Current Opinion in Hematology·Sophie PaczesnyJames L M Ferrara
Oct 27, 2009·Transplantation·Jean Kwun, Stuart J Knechtle
Feb 4, 2011·Science Translational Medicine·Damien Bresson, Matthias von Herrath
Oct 3, 2002·Annual Review of Medicine·Georgia B VogelsangDebra M Bensen-Kennedy
Nov 21, 2007·Hematology·Daniel Weisdorf
Mar 23, 2006·Blood·Corey CutlerEdwin Alyea
Jan 20, 2007·Blood·H Joachim Deeg
Sep 3, 2009·Blood·Helen E Heslop
Jan 18, 2008·World Journal of Gastroenterology : WJG·Patricia L Kozuch, Stephen B Hanauer
Nov 8, 2011·Immunotherapy·Ben SprangersChantal Mathieu
Mar 17, 2007·The Journal of Dermatological Treatment·Amir A ToorKenneth B Gordon
Oct 23, 2008·Expert Review of Hematology·John Koreth, Joseph H Antin
Feb 21, 2007·Expert Opinion on Biological Therapy·Ivo Van WalleIgnace Lasters
Mar 22, 2006·Expert Opinion on Biological Therapy·Michael H AlbertXue-Zhong Yu
Feb 28, 2003·Expert Opinion on Investigational Drugs·Jeffrey A Tuvlin, Sunanda V Kane
Dec 10, 2003·Expert Opinion on Emerging Drugs·David A Jacobsohn
May 25, 2004·Expert Opinion on Investigational Drugs·Martin Braddock
Dec 5, 2012·Seminars in Oncology·Onder Alpdogan, Marcel R M van den Brink
Jun 19, 2012·The Medical Clinics of North America·Daan DierickxAndré Delannoy
Jul 31, 2009·Science in China. Series C, Life Sciences·Liang Wang, Robert ChunHua Zhao
Nov 17, 2009·International Immunopharmacology·Ming LvBeifen Shen
Dec 17, 2008·Clinical Lymphoma & Myeloma·Oscar B Goodman, Nam H Dang
Jul 1, 2008·Current Opinion in Immunology·Patrick G SwannKathleen A Clouse

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