Application of polypeptide for inhibiting tumor immune escape

Abstract

The invention provides an application of a polypeptide for inhibiting tumor immune escape. The A11 polypeptide is a peptide derived from 20 to 30 sites of amino acids at the amino terminal of annexin A1 (ANXA1) (EYVQTVKSSKG). A series of experiments prove that the A11 polypeptide enters tumor cells by means of cell-penetrating peptide CPP (YGRKKRRQRRR), is competitively combined with deubiquitination enzyme USP7 to PD-L1, increases ubiquitination degradation of PD-L1, remarkably reduces the level of breast cancer, lung cancer and melanoma cells PD-L1, inhibits tumor immune escape, and plays an anti-tumor role in vitro and in vivo of mice. In addition, the A11 monoclonal antibody and the PD-1 monoclonal antibody (mAb) are jointly applied in a mouse body and have a synergistic anti-tumor immune escape effect. Therefore, the A11 polypeptide can be used as a new strategy of immune checkpoint blocking treatment, is used for tumor immunotherapy, and has important clinical application value.

Description

technical field [0001] The invention belongs to the technical field of drug development and treatment for inhibiting tumor immune escape, in particular to the application of an A11 polypeptide that targets down-regulating PD-L1 expression, blocking immune checkpoints and inhibiting tumor immune escape. Background technique [0002] Immune checkpoints are immune system brakes composed of receptor-ligand molecules, which negatively regulate immune responses and play a key role in maintaining immune tolerance and regulating the strength of immune responses. Tumor cells use immune checkpoints to negatively regulate immune responses and evade the monitoring of the body's immune system. [0003] Programmed death ligand 1 (PD-L1; also known as B7-H1) is a member of the B7 family of type I transmembrane protein receptors, encoded by the CD274 gene. Programmed death protein 1 (PD-1; also known as CD279) is a PD-L1 receptor expressed on the surface of T cells. PD-L1 is widely expres...

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