itolizumab + corticosteroids

**Itolizumab + corticosteroids** is a combination therapy consisting of itolizumab, a humanized IgG1 monoclonal antibody targeting CD6, and systemic corticosteroids. This regimen is under investigation for the first-line treatment of acute graft-versus-host disease (aGVHD) in patients who have undergone allogeneic hematopoietic stem cell transplantation.\n- **Itolizumab** acts by binding to CD6 on T cells, modulating T-lymphocyte activation and proliferation via interruption of the CD6-ALCAM co-stimulation pathway. This results in inhibition of T effector cell activity and reduced trafficking to target organs, with a marked reduction in multiple pro-inflammatory cytokines, particularly those associated with Th-1 and Th-17 pathways, such as IL-2, IFN-γ, TNF-α, and IL-6[2][4][8]. Itolizumab does not cause T- or B-cell depletion but reduces T-cell activation and trafficking by promoting CD6 receptor shedding and downstream signaling inhibition, impacting MAPK and STAT-3 pathways as well[2][4][8].\n- **Corticosteroids** are a standard first-line immunosuppressive therapy for aGVHD, typically administered as high-dose methylprednisolone or equivalent. They act through broad suppression of inflammatory gene expression via glucocorticoid receptor activation, inhibiting multiple inflammatory pathways and cytokine production.\n\nThe combination is currently being evaluated as an initial therapy for subjects with grade III-IV aGVHD, or grade II with lower GI involvement. The EQUATE and EQUATOR phase 1b/2 and phase 3 clinical trials use intravenous itolizumab alongside high-dose corticosteroids as the standard-of-care backbone[1][3][5][7].