Warning: Undefined array key "mm" in /www/wwwroot/www.ai-bt.com/si.php on line 10 Deprecated: trim(): Passing null to parameter #1 ($string) of type string is deprecated in /www/wwwroot/www.ai-bt.com/si.php on line 10 The storm has cleared: lessons from the CD28 superagonist TGN1412 trial.

Literature DB >> 22487653

The storm has cleared: lessons from the CD28 superagonist TGN1412 trial.

Abstract

The life-threatening cytokine-release syndrome suffered by six volunteers in a Phase I clinical trial following administration of the CD28 superagonist antibody TGN1412 (developed by TeGenero) in March 2006 was completely unpredicted by the preclinical studies. Here, Thomas Hünig, main founder of TeGenero, describes the recent investigations into what went wrong and discusses the lessons learnt for future clinical trials.

Entities: Gene

Mesh：

Substances：

Year: 2012 PMID： 22487653 DOI： 10.1038/nri3192

Source DB: PubMed Journal: Nat Rev Immunol ISSN： 1474-1733 Impact factor: 53.106

14 in total

1. Preculture of PBMCs at high cell density increases sensitivity of T-cell responses, revealing cytokine release by CD28 superagonist TGN1412.

Authors: Paula S Römer; Susanne Berr; Elita Avota; Shin-Young Na; Manuela Battaglia; Ineke ten Berge; Hermann Einsele; Thomas Hünig
Journal: Blood Date: 2011-09-19 Impact factor: 22.113

2. Monoclonal antibody TGN1412 trial failure explained by species differences in CD28 expression on CD4+ effector memory T-cells.

Authors: D Eastwood; L Findlay; S Poole; C Bird; M Wadhwa; M Moore; C Burns; R Thorpe; R Stebbings
Journal: Br J Pharmacol Date: 2010-10 Impact factor: 8.739

3. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412.

Authors: Ganesh Suntharalingam; Meghan R Perry; Stephen Ward; Stephen J Brett; Andrew Castello-Cortes; Michael D Brunner; Nicki Panoskaltsis
Journal: N Engl J Med Date: 2006-08-14 Impact factor: 91.245

4. Toward experimental assessment of receptor occupancy: TGN1412 revisited.

Authors: Zoe Waibler; Linda Y Sender; Christel Kamp; Jan Müller-Berghaus; Bernd Liedert; Christian K Schneider; Johannes Löwer; Ulrich Kalinke
Journal: J Allergy Clin Immunol Date: 2008-09-20 Impact factor: 10.793

Review 5. Manipulation of regulatory T-cell number and function with CD28-specific monoclonal antibodies.

Authors: Thomas Hünig
Journal: Adv Immunol Date: 2007 Impact factor: 3.543

6. CD28-mediated induction of proliferation in resting T cells in vitro and in vivo without engagement of the T cell receptor: evidence for functionally distinct forms of CD28.

Authors: M Tacke; G Hanke; T Hanke; T Hünig
Journal: Eur J Immunol Date: 1997-01 Impact factor: 5.532

7. Efficient expansion of regulatory T cells in vitro and in vivo with a CD28 superagonist.

Authors: Chia-Huey Lin; Thomas Hünig
Journal: Eur J Immunol Date: 2003-03 Impact factor: 5.532

8. Release of tumor necrosis factor, interleukin-2, and gamma-interferon in serum after injection of OKT3 monoclonal antibody in kidney transplant recipients.

Authors: D Abramowicz; L Schandene; M Goldman; A Crusiaux; P Vereerstraeten; L De Pauw; J Wybran; P Kinnaert; E Dupont; C Toussaint
Journal: Transplantation Date: 1989-04 Impact factor: 4.939

9. Rapid regulatory T-cell response prevents cytokine storm in CD28 superagonist treated mice.

Authors: Tea Gogishvili; Daniela Langenhorst; Fred Lühder; Fernando Elias; Karin Elflein; Kevin M Dennehy; Ralf Gold; Thomas Hünig
Journal: PLoS One Date: 2009-02-27 Impact factor: 3.240

10. Inhibition of ZAP-70 kinase activity via an analog-sensitive allele blocks T cell receptor and CD28 superagonist signaling.

Authors: Susan E Levin; Chao Zhang; Theresa A Kadlecek; Kevan M Shokat; Arthur Weiss
Journal: J Biol Chem Date: 2008-03-31 Impact factor: 5.157

57 in total

Review 1. The immunological synapse.

Authors: Michael L Dustin
Journal: Cancer Immunol Res Date: 2014-11 Impact factor: 11.151

Review 2. T-cell costimulatory blockade in organ transplantation.

Authors: Jonathan S Maltzman; Laurence A Turka
Journal: Cold Spring Harb Perspect Med Date: 2013-12-01 Impact factor: 6.915

3. Afterword: returning to philosophical foundations in research ethics.

Authors: Nir Eyal
Journal: J Med Ethics Date: 2016-06-27 Impact factor: 2.903

4. The return of the prodigal son and the extraordinary development route of antibody TGN1412 - lessons for drug development and clinical pharmacology.

Authors: Marcel J H Kenter; Adam F Cohen
Journal: Br J Clin Pharmacol Date: 2015-04 Impact factor: 4.335

5. Unregulated antigen-presenting cell activation by T cells breaks self tolerance.

Authors: Jaeu Yi; Jisun Jung; Sung-Wook Hong; Jun Young Lee; Daehee Han; Kwang Soon Kim; Jonathan Sprent; Charles D Surh
Journal: Proc Natl Acad Sci U S A Date: 2018-12-31 Impact factor: 11.205

6. Storm forecasting: additional lessons from the CD28 superagonist TGN1412 trial.

Authors: Christopher Horvath; Laura Andrews; Andreas Baumann; Lauren Black; Diann Blanset; Joy Cavagnaro; Kenneth L Hastings; David L Hutto; Timothy K MacLachlan; Mark Milton; Theresa Reynolds; Stan Roberts; Mark Rogge; Jennifer Sims; George Treacy; Garvin Warner; James D Green
Journal: Nat Rev Immunol Date: 2012-08-31 Impact factor: 53.106

10. Agonistic TAM-163 antibody targeting tyrosine kinase receptor-B: applying mechanistic modeling to enable preclinical to clinical translation and guide clinical trial design.

Authors: Yulia Vugmeyster; Cynthia Rohde; Mylene Perreault; Ruth E Gimeno; Pratap Singh
Journal: MAbs Date: 2013-03-25 Impact factor: 5.857