Itolizumab is a clinical-stage, first-in-class immune-modifying monoclonal antibody that targets the CD6-ALCAM signaling pathway to selectively downregulate pathogenic T effector cells while preserving T regulatory cells critical for maintaining a balanced immune response.

Activated T effector cells drive a number of immuno-inflammatory diseases across therapeutic areas including transplant science, systemic autoimmunity, pulmonary, neurologic, gastrointestinal, renal, vascular, ophthalmic and dermatologic disorders and we believe itolizumab may have broad therapeutic utility in treating a large and diverse set of T cell mediated diseases.

In preclinical studies, blockade of CD6 with itolizumab led to a reduction in T effector cell proliferation and downregulation of several important pathways that contribute to T effector cell development. The downregulation of these pathways is accompanied by decreased secretion of the pro-inflammatory T effector cytokines IFN-γ, TNF-α, IL-6 and IL-17. Additionally, inhibiting the binding of ALCAM to CD6 modulates lymphocyte trafficking and results in reduced T effector cell infiltration into inflamed tissues.

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thumbnail for Itolizumab uniquely modulates both the activity and trafficking of T effector cells video
Krishna Polu, M.D., Equillium’s former Chief Medical Officer, discusses how itolizumab uniquely modulates both the activity and trafficking of teff cells.

Autoimmunity Is a Balancing Act

The role of the immune system is to defend the body against foreign organisms and cells, and in doing so it must distinguish accurately between self and non-self entities, a process called tolerance. Autoimmunity is an immune response directed against the body’s own healthy cells and tissues, and is the underlying process in many inflammatory diseases. Autoimmunity results from a loss of tolerance caused in part by an imbalance in the relationship between Teff cells and regulatory T cells (Treg cells).

Thumbnail for Role of T cells in health and disease video
Stephen Connelly, Ph.D., Equillium’s Chief Scientific Officer, discusses the role of T cells in modulating immune responses.



Thumbnail for Role of T cells in health and disease video
Stephen Connelly, Ph.D., Equillium’s Chief Scientific Officer, discusses the role the CD6-ALCAM pathway plays in the activity and trafficking of Teff cells.

The CD6-ALCAM Pathway Plays a Central Role in Autoimmunity

CD6 is a co-stimulatory receptor that uniquely modulates T cell activity and trafficking and is a key checkpoint in regulating Teff cells that are central to autoimmune responses. Activated leukocyte cell adhesion molecule (ALCAM) is a ligand of CD6 that is expressed on hematopoietic tissues such as antigen-presenting cells, where it is important for immune synapse formation and optimal co-stimulation. Binding of ALCAM to CD6 leads to the downstream activation of several mitogen activated protein kinase (MAPK) pathways related to T cell activation, proliferation, differentiation and survival. Preclinical and clinical studies have shown that blockade of the CD6-ALCAM pathway leads to selective inhibition of pathogenic Teff cell activity and trafficking, while preserving the important regulatory function of Treg cells, which provide ongoing immune surveillance.


CD6-ALCAM Pathway Central to Immuno-inflammation

Itolizumab Inhibits Pathogenic T Cell Activity & Trafficking