Introduction of Zanolimumab

Zanolimumab is a high affinity human monoclonal antibody and an immunosuppressive drug targeting the CD4-molecule. It was developed for the treatment of rheumatoid arthritis, psoriasis, melanoma, cutaneous and peripheral T-cell lymphoma. Zanolimumab has previously been assessed in clinical trials in the therapy of inflammatory diseases like psoriasis and rheumatoid arthritis, where a favorable safety profile has been demonstrated. Although good tolerability was demonstrated, studies were discontinued in this field because of lack of significant efficacy. The significant T cell depletion in these trials promised benefit in malignant T cell disorders and therefore zanolimumab entered into clinical studies for these indications.

Mechanism of Action of Zanolimumab

Zanolimumab is a human monoclonal antibody specific for the CD4 antigen, which is expressed on a subset of T cells in rheumatoid arthritis, psoriasis, melanoma, cutaneous and peripheral T-cell lymphoma. Due to the interference with the interaction of the CD4 antigen and the major histocompatibility complex class II-molecule (MHC-II), this antibody dose-dependently decreases T cell activation. Zanolimumab inhibits CD4⁺ T cells by combining signaling inhibition with potent induction of Fc-mediated effector functions. T cell activation is inhibited by a fast dual mechanism in which the antibody abrogates signaling via the T cell receptor (TCR) and, in addition, down regulates T cell activation by transmission of direct inhibitory signals. In addition, zanolimumab induces killing of CD4+ T cells via antibody-dependent cellular cytotoxicity (ADCC) with no additional complement-dependent cytotoxicity (CDC).

Fig.1 Mechanism of action of zanolimumab

For research use only. Not intended for any clinical use.