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Treatment of cancer harboring mutations in the tp53 gene and/or post-translational modifications in the p53 protein with parvoviruses

A cancer and gene technology, applied in the field of oncology, can solve problems such as complex mechanism of action

Pending Publication Date: 2021-11-19
AUTONOMOUS UNIVERSITY OF MADRID
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

5-Fluorouracil has a complex mechanism of action, including alterations in heterochromatin and RNA metabolism
However, oncolytic viruses that selectively act on cancers carrying TP53 mutations and / or post-translational modifications of the p53 protein have not been found in the prior art
In other words, the capacity of oncolytic viruses has so far not been specifically linked to mutations in the TP53 gene and / or post-translational modifications of the p53 protein

Method used

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  • Treatment of cancer harboring mutations in the tp53 gene and/or post-translational modifications in the p53 protein with parvoviruses
  • Treatment of cancer harboring mutations in the tp53 gene and/or post-translational modifications in the p53 protein with parvoviruses
  • Treatment of cancer harboring mutations in the tp53 gene and/or post-translational modifications in the p53 protein with parvoviruses

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0063] Example 1. Materials and methods

Embodiment 11

[0064] Example 1.1. Cells and cell culture.

[0065] Human glioblastoma stem cells were obtained from tumor explants provided by the Neurosurgery Service of Ramón y Caial Hospital, Madrid. The explants were diagnosed as grade IV glioblastoma by histochemistry performed by the pathology service at the same hospital. Informed consent from the patients was obtained in all cases and approval was obtained from the Institutional Ethics Committee of the Ramón y Caial Hospital, Madrid. Further studies in tissue culture were authorized by the Ethics Committee of the University of Madrid and the Center for Molecular Biology of Severo Ochoa (Centrode Biología Molecular Severo Ochoa, CSIC-UAM), respectively. Biopsies collected at the bottom of the operating room were dissociated mechanically and enzymatically, and finally the cell suspension was filtered to culture in DMEM medium: F12 (1:1) supplemented with various factors.

[0066] On the other hand, established mouse, human cancer an...

Embodiment 12

[0077] Example 1.2. Flow Cytometry.

[0078]In all experiments, at least 30,000 events / sample were acquired in a FACS CantoII cytometer (BD Biosciences), which were preselected in a region based on their size and complexity (FSC and SSC parameters, respectively) to exclude cells Debris and other contamination particles. Events were acquired using CellQuest software (BD Biosciences) and data were analyzed using FlowJo software (Tree Star). Cell cycle analysis was performed according to [Gil-Ranedo, J., Hernando, E., Riolobos, L., Dominguez, C., Kann, M., and José M. Almendral. 2015. The mammalian cell cycle regulates nuclear parvovirus capsid assembly. Plos Pathogens, 11;11(6):e1004920]. For staining, cells were permeabilized with PBS+0.1% tritonX-100 for 10 min at room temperature and then blocked with the same buffer supplemented with 1% FCS for 20 min. Cells were resuspended in PBS (pH 7.2) + 0.5% BSA, primary antibodies indicated in the figure were added, and stirred at ...

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Abstract

Treatment of cancer harboring mutations in the TP53 gene and / or post-translational modifications in the p53 protein. The present invention relates to the use of viruses belonging to the family Parvoviridae, genus Protoparvovirus, or combinations of such viruses with chemotherapy drugs, in the treatment of cancer. In particular the cancer is characterized by showing mutations in the TP53 gene and / or post-translational modifications in the p53 protein.

Description

technical field [0001] The present invention is included in the field of oncology. In particular, the present invention relates to the use of viruses belonging to the family Parvoviridae, preferably belonging to the genus Protoparvovirus, or combinations of such viruses with chemotherapy, for the treatment of cancer. In particular, cancers are characterized by the presence of mutations in the TP53 gene and / or post-translational modifications of the p53 protein. Background technique [0002] p53 protein and cancer [0003] The p53 protein, expressed by the TP53 gene, plays an important role in controlling the cell cycle and genome stability through very different mechanisms, which is why the p53 protein is sometimes referred to as the "guardian of the genome." It is therefore not surprising that mutations in the TP53 gene are one of the main mechanisms leading to many different types of cancer in humans. In fact, TP53 is the most frequently mutated gene in human cancers, a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K35/768A61P35/00
CPCA61K35/768A61K45/06A61P35/00C12N2750/14332C12N2750/14021C12N2750/14051C12N2750/14022C12N7/00C07K14/4746Y02A50/30
Inventor 何塞·玛丽亚·阿尔门德罗·德·里奥卡洛斯·加勒戈乔恩·吉尔-拉内多
Owner AUTONOMOUS UNIVERSITY OF MADRID
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