From TGN1412 to TAB08: the return of CD28 superagonist therapy to clinical development for the treatment of rheumatoid arthritis.

Abstract

CD28 superagonists (CD28SA) are CD28-specific monoclonal antibodies which are able to activate T-cells without overt TCR engagement. In rodents, CD28SA efficiently activate regulatory T-cells and are therapeutically effective in multiple models of autoimmunity, inflammation and transplantation. However, a phase I study of the human CD28SA TGN1412 in 2006 resulted in a life-threatening cytokine storm. This brief review summarises preclinical work before and since the failed phase I trial with an emphasis on understanding the reasons why there had been no warning of toxicity, and how a novel assay paved the way for a new phase I, phase Ib (both completed), and an ongoing phase II study.

• Authors: Dmitry Tyrsin, Sergey Chuvpilo, Alexey Matskevich, Daniil Nemenov, Paula S Römer, Paula Tabares, Thomas Hünig
• Journal: Clinical and experimental rheumatology (Clin Exp Rheumatol) 2016 Jul-Aug Vol. 34 Issue 4 Suppl 98 Pg. 45-8 ISSN: 0392-856X [Print] Italy
• PMID: 27586803 (Publication Type: Journal Article, Review)

Chemical References

• Antibodies, Monoclonal, Humanized
• Antirheumatic Agents
• CD28 Antigens
• Cytokines
• TGN-1412

Topics

• Animals
• Antibodies, Monoclonal, Humanized (adverse effects)
• Antirheumatic Agents (adverse effects)
• Arthritis, Rheumatoid (drug therapy, immunology, metabolism)
• CD28 Antigens (antagonists & inhibitors, immunology, metabolism)
• Cytokines (immunology, metabolism)
• Disease Models, Animal
• Humans
• Lymphocyte Activation (drug effects)
• Molecular Targeted Therapy
• Risk Assessment
• Signal Transduction (drug effects)
• T-Lymphocytes, Regulatory (drug effects, immunology, metabolism)