Itolizumab – a humanized anti-CD6 monoclonal antibody with a better side effects profile for the treatment of psoriasis

Abstract

Management of psoriasis is a challenge to the treating physician. The chronic inflammatory state of psoriasis with exacerbations and remissions necessitate “on-and-off” treatment schedules. The safety profiles of drugs and tolerability issues for patients are important factors to be considered during treatment. Various biological agents targeting T-cells and the inflammatory cytokines are available for systemic treatment of psoriasis. However, major causes of concern while using these drugs are risk of susceptibility to infection and development of anti-drug antibodies, which will affect the pharmacokinetic properties, efficacy, and safety profile of the drug. Itolizumab, a humanized anti-CD6 monoclonal antibody, is a new molecule that acts by immunomodulating the CD6 molecule. CD6 is a co-stimulatory molecule required for optimal T-cell stimulation by the antigen-presenting cells. This step is crucial in T-cell proliferation to form Th1 and Th17 cells, which play a major role in the pathogenesis of psoriasis. This article deals with the properties of Itolizumab and its role in the treatment of psoriasis. Based on the available published data, Itolizumab seems to have a better adverse effects profile and at the same time comparatively less efficacy when compared to other biological agents available for treating psoriasis. Larger studies with longer duration are required to clearly depict the long-term side effects profile.

CD6 monoclonal antibodies differ in epitope, kinetics and mechanism of action

“…In the first clinical use of CD6 mAbs, the major mode of action was generally attributed to elimination of cells . More recently, it has been proposed that a therapeutic CD6 mAb is efficacious by perturbing CD6 function and that depletion is not the major mode of action . Among the leucocyte receptors, CD6 has the longest cytoplasmic region without catalytic activity so there is potential for significant modulation of signalling.…”

“…For the development of therapeutic modulation of CD6 activity it is imperative to understand how the pleiotropic effects of CD6 are regulated. A CD6 mAb, itolizumab, is now licensed for use to treat autoimmune disease and there is evidence that it is less toxic but also less effective than other reagents . It is important to understand how CD6 mAbs perturb function if their use in immunotherapy is to be rationally optimized.…”

“…Itolizumab (Alzumab™) has been developed as a therapeutic drug for the treatment of psoriasis. It has been exploited for clinical use based on its immunosuppressive effects . In a study of 26 psoriasis patients receiving multiple injections of the humanized version of ior t1, itolizumab, over the course of a year, the mAb was immunosuppressive; the reduction of the proliferation and production of pro‐inflammatory cytokines being statistically significant .…”

Clinical Outcome of a Novel Anti-CD6 Biologic Itolizumab in Patients of Psoriasis with Comorbid Conditions

“…Itolizumab acts by specifically binding to CD6 epitope, a surface protein of T cells, which is essential for optimum T-cell activation by the antigen-presenting cells. Formation of helper Th1 and Th17 cells and releasing of cytokines is an important phase in T-cell proliferation [9]. …”

“…It acts upstream by inhibiting the costimulation of T cells results in decreasing release of signature cytokines of Th1 and Th17 cells [9]. Here we are presenting the response indicated by Itolizumab in 7 Indian patients having moderate-to-severe psoriasis with severe comorbidities and who were intolerant/nonresponding to conventional therapies.…”