Fully humanized single-domain antibody for human TIM-3 (T cell immunoglobulin and mucin-3) and applications

Abstract

The invention belongs to the biotechnological field and particularly relates to a fully humanized single-domain antibody for human TIM-3 (T cell immunoglobulin and mucin-3), an antigen combing fragment of the antibody and applications of the antibody and the antigen combining fragment. The invention discloses the fully humanized single-domain antibody for the immune checkpoint molecule TIM-3 and the antigen combing fragment of the antibody. The single-domain antibody is mainly characterized by being determined by a CDR (complementarity-determining region) specific gene sequence existing in anantibody heavy chain gene variable region, and the effectively expressed antibody specifically combined with the TIM-3 is obtained from prokaryotic and eukaryotic cells. Different forms of geneticallyengineered antibodies can be modified and produced in prokaryotic and eukaryotic cells and any expression system by use of the CDR or partial or full gene of the body, and the antibody can be used for preparing preparations for clinical diagnosis or treatment of autoimmune diseases, chromic virus infection, tumor and other diseases.

Description

technical field [0001] The invention belongs to the field of biotechnology, and in particular relates to a fully human single-domain antibody against human TIM-3, an antigen-binding fragment thereof, and applications thereof. Background technique [0002] T cell immunoglobulin and mucin-3 (T cell immunoglobulin and mucin-3, TIM-3) was first discovered in activated T helper cell 1 (Th1) in 2002, and belongs to the TIM family member, human TIM-3 The molecule is a type I membrane protein consisting of 301 amino acids. The TIM-3 is an important negative regulatory molecule, which can bind to its ligand galectin-9 (Galectin-9), inhibit the expansion of Th1 and Th17 cells, promote Th1 apoptosis, CD8 + Exhaustion of T cells induces massive expansion of myeloid-derived suppressor cells (MDSCs), thereby directly and / or indirectly promoting peripheral immune tolerance and inhibiting the body's anti-tumor immunity. Later, it was found that TIM-3 is also expressed on the surface of n...

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Problems solved by technology

[0003] However, the molecular weight of the full-length monoclonal antibody is too large (150 kDa), which leads to some significant defects in its clinical application: First, the excessive molecular weight results in poor permeability of tissues (such as the blood-brain barrier), which

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