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A recombinant oncolytic adenovirus carrying human membrane-penetrating peptide p53 and gm-csf genes and its use

An oncolytic adenovirus, p53 gene technology, applied in the field of recombinant oncolytic adenovirus, can solve the problems of low therapeutic index, large toxic and side effects, difficult to receive curative effect and the like

Active Publication Date: 2016-09-07
HEPATOBILIARY SURGERY HOSPITAL SECOND MILITARY MEDICAL UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

At present, the conventional treatment of malignant tumors is difficult to receive the expected curative effect, especially the therapeutic index of chemotherapy drugs is low, and the side effects are large

Method used

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  • A recombinant oncolytic adenovirus carrying human membrane-penetrating peptide p53 and gm-csf genes and its use
  • A recombinant oncolytic adenovirus carrying human membrane-penetrating peptide p53 and gm-csf genes and its use
  • A recombinant oncolytic adenovirus carrying human membrane-penetrating peptide p53 and gm-csf genes and its use

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Embodiment Construction

[0043] The term "p53" is also called Tp53. The official ID number of the NCBI gene bank is 7157. It is a transcription factor that controls the initiation of the cell cycle. In all malignant tumors, more than 50% of the gene mutations will occur. The functions of p53 include: arresting cell cycle; promoting cell apoptosis; maintaining genome stability; inhibiting tumor angiogenesis, etc. At the same time, p53 can effectively enhance immune response and is a good tumor vaccine.

[0044] The p53 gene (official name TP53, ID number 7157) has multiple isoforms, namely NM_000546.5 / NP_000537.3 (cDNA sequence / protein sequence), NM_001126112.2 / NP_001119584.1, NM_001126113.2 / NP_001119585.1 ,NM_001126114.2 / NP_001119586.1,NM_001126115.1 / NP_001119587.1,NM_001126116.1 / NP_001119588.1,NM_001126117.1 / NP_001119589.1,NM_001126118.1 / NP_001119590.1,NM_001276695.1 / NP_001263624.1,NM_001276696 .1 / NP_001263625.1,NM_001276697.1 / NP_001263626.1,NM_001276698.1 / NP_001263627.1,NM_001276699.1 / NP_001263628.1...

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Abstract

The invention belongs to genetic engineering and oncology, and relates to a recombinant oncolytic adenovirus containing human penetrating peptide p53 gene and GM-CSF gene and its application. Specifically, the present invention relates to a recombinant oncolytic adenoviral vector, which is operably inserted into or contains the following exogenous genes: a penetrating peptide coding sequence, a p53 gene or its degenerate sequence, a 2A linker sequence, and GM-CSF Gene or its degenerate sequence. The present invention also relates to a recombinant oncolytic adenovirus containing the recombinant oncolytic adenoviral vector. The recombinant oncolytic adenovirus of the present invention can efficiently infect tumor cells (including tumor stem cells), specifically proliferate in tumor cells, lyse tumor cells, and efficiently express human membrane-penetrating peptide p53 and GM-CSF proteins to promote tumor cell apoptosis. And play an anti-tumor effect by enhancing the immune response. The recombinant oncolytic adenovirus provided by the invention can be used for the treatment of various types of malignant tumors.

Description

technical field [0001] The invention belongs to genetic engineering and oncology, and relates to a recombinant oncolytic adenovirus containing human penetrating peptide p53 gene and GM-CSF gene and its application. Background technique [0002] Malignant tumors are a large class of diseases that seriously threaten human life and health. With the development of society and economy, the main risk factors of tumors have not been effectively controlled, but intensified, and the morbidity and mortality continue to rise. At present, the conventional treatment of malignant tumors is difficult to receive the expected curative effect, especially the therapeutic index of chemotherapy drugs is low and the side effects are large. In recent years, biological therapy including gene therapy has become an indispensable part of tumor clinical practice. my country's recombinant adenovirus p53 injection "Ad-p53" was launched in 2004, becoming the world's first marketed cancer gene therapy dru...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N15/861C12N7/01C12N15/33A61K48/00A61K35/761A61P35/00
Inventor 钱其军金华君吕赛群吴红平丁娜俞德超刘辉李林芳吴孟超
Owner HEPATOBILIARY SURGERY HOSPITAL SECOND MILITARY MEDICAL UNIV