Antibodies to the C-type lectin, L-SIGN, as tentative therapeutic agents for induction of antigen-specific tolerance

Abstract

Antigen-presenting cells (APCs), which capture and process antigens for presentation to T cells, are critical in initiating not only T cell immune responses, but also T cell tolerance. APCs express calcium-dependent carbohydrate-binding proteins called C-type lectin receptors that bind and internalize antigens. An important class of such receptors is represented by dendritic cell-specific intercellular adhesion molecule-grabbing non-integrin (DC-SIGN) and its close homolog, liver specific-SIGN (L-SIGN). Whereas DC-SIGN is predominantly expressed on DCs and macrophages, L-SIGN is mostly expressed on liver and lymph node sinusoidal endothelial cells (SECs), a specialized population of non-myeloid APCs that is thought to be primarily involved in immune tolerance. Thus, it has been postulated that targeting an antigen to SECs via L-SIGN may induce tolerance to this antigen. To that aim, the present application describes novel L-SIGN specific antibodies that are rapidly internalized within SECs upon binding to L-SIGN. It is claimed that these antibodies may be linked to an autoantigen for selective delivery to SECs, which might provide a potential therapeutic strategy to promote autoantigen-specific T cell tolerance in the treatment of autoimmunity.

Keywords::

• antigen-presenting cell
• antibody
• C-type lectin
• dendritic cells
• DC-SIGN
• immune tolerance
• immunotherapy
• L-SIGN
• microbial pathogen recognition
• sinusoidal endothelial cell
• T cell

Patent Details

• Title Method of treating autoimmune disease by inducing antigen presentation by tolerance inducing antigen-presenting cells.

• Assignee Alexion Pharmaceuticals, Inc.

• Inventors Bowdish KS, Kretz-Rommel A, Dakappagari N.

• Priority date 17/12/04.

• Filing date 16/12/05.

• Publication date 13/07/06.

• Publication no. WO2006073748.