Recombinant TRAIL-Fc fusion protein as well as preparation and application thereof

Abstract

The invention relates to a design technology for fusion protein and a protein expression and purification technology, and relates the application of fusion protein as a tumor therapeutic medicament. The invention is characterized by fusing the 114th-281th amino acid of tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL) with human IgGlFc. The fused protein consists of 400 amino acids, the isoelectric point pI is 9.34, and theoretical molecular weight is 45535.30. The protein exists by a dimer or a trimer, can remarkably induce apoptosis of a plurality of kinds of tumor cellsand kills or / and inhibit tumor cells in an animal body. Compared with TRAIL, the TRAIL-Fc fusion protein has large molecular weight, high activity and long vivo half-life, is expressed by mammalian cells, and can be used as a tumor therapeutic medicament.

Description

technical field The invention belongs to the field of biotechnology, and in particular relates to a TRAIL-Fc fusion protein design technology and a protein expression and purification technology, and relates to the application of the fusion protein as a tumor treatment drug. Background technique TRAIL (TNF-Related Apoptosis Inducing Ligand), that is, tumor necrosis factor-related apoptosis-inducing ligand, is a member of the TNF superfamily. Human TRAIL is a type II transmembrane protein, that is, its C-terminus is outside the membrane, while its N-terminus is inside the cell. TRAIL consists of 281 amino acids, its molecular weight is 32KD, and its extracellular region consists of 243 amino acids. The physiological function of TRAIL is to induce apoptosis. Although TRAIL is expressed in many normal cells such as cardiomyocytes, lymphocytes, spleen cells, prostate cells, ovarian cells and small intestinal cells, it only induces tumor cells and virus-transformed cells. Apopt...

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Problems solved by technology

However, since the half-life of TRAIL in plasma is only about 30 minutes, cancer patients need to be administered daily and the dosage is relatively large (15mg / kg / d), so it is necessary to prolong its half-life in plasma

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