Theralizumab

Theralizumab
Monoclonal antibody
TypeWhole antibody
SourceHumanized (from mouse)
TargetCD28
Clinical data
Routes of
administration		intravenous
ATC code
  • none
Legal status
Legal status
  • not approved by any regulatory agency, highly toxic
Identifiers
CAS Number
ChemSpider
  • none
UNII
  (verify)

Theralizumab (also known as TGN1412, CD28-SuperMAB, and TAB08) is an immunomodulatory drug developed by immunologist Thomas Hünig of the University of Würzburg. It was withdrawn from development after inducing severe inflammatory reactions as well as chronic organ failure in the first-in-human study by Parexel in London in March 2006.[1] The developing company, TeGenero Immuno Therapeutics (TeGenero), a spin-off of the University of Würzburg around immunologist Thomas Hünig, co-founder and chief scientific officer (CSO) Thomas Hanke and chief executive officer (CEO) Benedikte Hatz went bankrupt later that year.[1][2][3] The commercial rights were then acquired by a Russian startup, TheraMAB.[4] The drug was renamed TAB08. Phase I and II clinical trials have been completed for arthritis[5] and clinical trials have been initiated for cancer.

Originally intended for the treatment of B cell chronic lymphocytic leukemia (B-CLL) and rheumatoid arthritis,[6] TGN1412 is a humanised monoclonal antibody that not only binds to, but is a strong agonist for, the CD28 receptor of the immune system's T cells.[7] CD28 is the co-receptor for the T cell receptor; It binds to receptors on the interacting partner in the reaction through one of its ligands (B7 family).

The drug, which was designated as an orphan medical product by the European Medicines Agency in March 2005, was developed by TeGenero, tested by Parexel and manufactured by Boehringer Ingelheim.[8][9] TeGenero announced the first elucidation of the molecular structure of CD28 almost exactly one year prior to commencement of the TGN1412 phase I clinical trial.

  1. ^ a b Goldacre B (2012). Bad Pharma. London: Fourth Estate. pp. 8–10, 104–105. ISBN 9780007350742.
  2. ^ Hünig, Thomas (18 May 2016). "The rise and fall of the CD 28 superagonist TGN 1412 and its return as TAB 08: a personal account". The FEBS Journal. 283 (18): 3325–3334. doi:10.1111/febs.13754. ISSN 1742-464X. PMID 27191544.
  3. ^ "Thomas Hanke". The Org (theorg.com). Archived from the original on 25 August 2024. Retrieved 25 August 2024.
  4. ^ Hirschler B (24 March 2015). "Exclusive: Drug that caused 'elephant man' side effect makes comeback after 2006 disaster". Reuters. Retrieved 26 November 2020.
  5. ^ "Safety, Tolerability, Pharmacodynamics and Efficacy Study of TAB08 in Patients With Rheumatoid Arthritis in Which Methotrexate (MTX) Treatment is Not Effective". ClinicalTrials.gov. US National Library of Medicine. 27 February 2017. Retrieved 1 July 2021.
  6. ^ TeGenero (20 February 2006). "Drug Development". TeGenero. Archived from the original on 12 April 2006. Retrieved 16 March 2006.
  7. ^ Lin CH, Kerkau T, Guntermann C, Trischler M, Beyersdorf N, Scheuring Y, Tony HP, Kneitz C, Wilhelm M, Mueller P, Huenig T (16 November 2004). "Superagonistic Anti-CD28 Antibody TGN1412 as a Potential Immunotherapeutic for the Treatment of B Cell Chronic Lymphocytic Leukemia". Blood (ASH Annual Meeting Abstracts). 104 (11): Abstract 2519. Archived from the original on 14 April 2013.
  8. ^ "TeGenero AG receives EU-orphan drug designation for Humanized Agonistic Anti-CD28 Monoclonal Antibody TGN1412 for the treatment of B-cell Chronic Lymphocytic Leukaemia, B-CLL" (PDF) (Press release). TeGenero. 13 March 2005. Archived from the original (PDF) on 19 March 2006.
  9. ^ "Boehringer Ingelheim and TeGenero sign agreement to develop and manufacture CD28-SuperMAB" (PDF) (Press release). TeGenero. 17 November 2003. Archived from the original (PDF) on 18 March 2006.