Description of Invention: Available for licensing and commercial development are methods to produce and/or enhance therapeutic agents based on models of the three-dimensional structures of the Ig-like domains of various TIM family members to a) develop agonists and antagonists of the T-cell immunoglobulin mucin (TIM) family of receptors and b) design specific TIM receptor-mutants with altered binding capabilities. The TIM receptors are involved in the regulation of immune responses, tissue regeneration, cancer, and viral cell entry. The invention provides models of the three-dimensional structures of the Ig-like domains of TIM family members developed after several crystal structures were resolved. The structures were further validated by mutagenesis and biochemical analysis.
The TIM family comprises type 1 integral membrane glycoproteins containing a characteristic six-cysteine Ig-like domain extended above the cell surface by a mucin-like domain. The crystal structures revealed diverse homophylic interactions between TIM family members. The three-dimensional structure of all TIM family members can be used in the making of agonists and antagonists of homophilic, heterophilic, and ligand interactions of these receptors.
Therapies that target the interaction of TIM family members with their ligands, such as small molecules or monoclonal antibodies, can control immune responses and the development of a variety of diseases.
TIM receptor-mutants with enhanced, reduced, or destroyed binding capabilities to ligands and TIM family receptors can control TIM receptor-functions.
Furthermore, the homophylic, heterophylic, and ligand interactions between the TIM receptors and the TIM receptor-mutants can be used as targets to develop therapeutic agents for medical and veterinary purposes, to prevent viral infection, regulate immune responses, modulate cell adhesion and tissue regeneration, treat and prevent cancer, and treat autoimmune and atopic diseases.
Development Status: The technology is in early stages of development.
C Santiago, A Ballesteros, C Tami, L Martínez-Munoz, GG Kaplan, JM Casasnovas. Structures of T cell immunoglobulin mucin receptors 1 and 2 reveal mechanisms for regulation of immune responses by the TIM receptor family. Immunity. 23 Mar 2007;26(3):299-310. [ PubMed abs ]
A Anderson, S Xiao, VK Kuchroo. Tim protein structures reveal a unique face for ligand binding. Immunity. 23 Mar 2007;26(3):273-275. [ PubMed abs ]
Licensing Status: Available for non-exclusive or exclusive licensing.
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