What was TGN1412 and its intended therapeutic use?

TGN1412 was described as an immunomodulatory humanized agonistic monoclonal antibody (MAB) directed against the CD28 protein of T lymphocytes. This drug was developed by a company TeGenero AG, based in Würzburg, Germany, and was manufactured by Boehringer Ingelheim.

TGN1412 belongs to one of the super-agonist MAB known to augment immune function, and a small number of them activate white blood cells autonomously. According to Kindt, Goldsby, and Osborne, T cell activation requires antigen receptor and corresponding T cell surface protein, CD28.

The latter gets stimulated by diffusible legends, and this results in cross-linking of the T antigen and CD28. Super-agonist MAB’s can replace the legends and give complete activation to T cells by binding to CD28.

Consequently, the activated T cells trigger a toxic storm of cytokines, which start to attack the body’s own tissue. TGN1412 was aimed to develop for the treatment of immunological diseases, multiple sclerosis, rheumatoid arthritis, and leukemia. Scientists working with this novel drug from TeGenero AG claimed that it binds to the conserved regions of CD28, common to rodents and humans. In a rat model, the MAB highly stimulated the T cell proliferation without causing any toxic effect.

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