Pluripotent stem cell expressing B7-H5 blocker or derivative and application thereof

Abstract

The invention discloses a pluripotent stem cell for expressing a B7-H5 blocker or a derivative of the pluripotent stem cell and application of the pluripotent stem cell, an expression sequence of the B7-H5 blocker is introduced into a genome of the pluripotent stem cell or the derivative of the pluripotent stem cell, and the B7-H5 blocker is an anti-B7-H5 antibody. The pluripotent stem cell expressing the B7-H5 blocker or the derivative of the pluripotent stem cell can be applied to low-immunogenicity cells such as iPSCs (induced pluripotent stem cells) induced by autologous cells or differentiated into MSCs (mesenchymal stem cells), can continuously express the B7-H5 blocker in vivo, and is used for treating B7-H5 high-expression tumors and related diseases.

Description

technical field [0001] The invention belongs to the technical field of genetic engineering, and specifically relates to a pluripotent stem cell expressing a B7-H5 blocker or a derivative thereof and an application thereof. Background technique [0002] B7-H5 (also known as: VISTA, Gi24, PD-1H or Dies1): is a type I membrane protein of about 55-65KD and belongs to the immunoglobulin superfamily. Consists of an IgV domain, a stem of about 30 amino acids, a transmembrane domain, and a cytoplasmic domain of 95 amino acids, and uniquely has 4 additional cysteine ​​residues, 3 of which are within the IgV domain, One is within the stem area. The cytoplasmic tail does not have the classic ITIM / ITAM motif, but the cytoplasmic tail has an SH2 domain in the middle. B7-H5 is mainly expressed on mature myeloid APC cells (antigen presenting cells) including macrophages, mature mouse bone marrow-derived dendritic cells (BMDC), neutrophils and CD11c DC cells and activated regulatory T cel...

AI Technical Summary

Problems solved by technology

However, for this kind of cells, firstly, the types of antigens presented by HLA-I antigens are reduced by more than two-thirds, and the integrity of the antigens that can be presented is greatly and irreversibly reduced. For various tumors, viruses and other disease antigens The presentation is highly biased, and still retains a considerable degree of risk of tumorigenesis and viral infection, and the risk of disease is higher when CIITA is knocked out at the same time; secondly, 12 high-frequency immune types The ethnic differences of HLA-C antigens are very large, and only 70% of them can be accounted for in some areas through our verification and calculation. However, China, India and other populous countries do not yet have authoritative large-sample HLA data. The use of PSCs is still subject to the test of a huge matching gap; third, this method will undergo several repeated gene editing work, and at least two rounds of single-cell isolation and culture for each gene editing, the whole process requires at least six rounds of single-cell isolation and culture. Cell separation and culture, these processes are inevitable and highly probable due to multiple gene editing off-targets or chromatin instability, or various unpredictable mutations in cells due to a large number of single-cell passages and proliferations, which in turn induce various problems such as carcinogenesis and metabolic diseases

It can be seen that this type of immune compatibility program is also an expedient measure in the "transitional period", and there are still many problems that have not been better resolved

[0008] In addition, some people have designed to induce killing of donor tissues and cells after they become diseased by inducing suicide genes. The loss of suitable donor cells, tissues and organs after killing is another big problem

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