Itolizumab (DB16207): A Comprehensive Monograph on a First-in-Class Anti-CD6 Immunomodulator

Executive Summary

[Itolizumab is a first-in-class, humanized IgG1 kappa monoclonal antibody that represents a novel approach to immunomodulation by selectively targeting the CD6 co-stimulatory receptor on T-cells. Developed jointly by the Center of Molecular Immunology in Cuba and Biocon in India, the drug has a bifurcated history of regional commercial success and significant developmental challenges in Western markets. It is approved and marketed in India under the brand name ALZUMAb™ for the treatment of moderate-to-severe chronic plaque psoriasis and, under a restricted emergency use authorization, for cytokine release syndrome (CRS) in patients with moderate-to-severe Acute Respiratory Distress Syndrome (ARDS) due to COVID-19.]

[The core of Itolizumab's therapeutic potential lies in its unique mechanism of action. It binds to the SRCR1 domain of CD6, modulating the interaction with its ligand, ALCAM, without directly blocking it. This results in the selective downregulation of pathogenic T effector cell (Teff) activity and proliferation, particularly of the Th1 and Th17 lineages, while preserving the function of crucial T regulatory cells (Tregs). This upstream intervention leads to a broad suppression of pro-inflammatory cytokines, including TNF-α, IFN-γ, IL-6, and IL-17. This selective mechanism is the biological foundation for the drug's most compelling clinical attribute: a consistently favorable safety profile characterized by a notably low risk of serious infections, a key differentiator from many existing biologics and immunosuppressants.]