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Method for reprogramming cancer cells into non-cancer cells in vivo and application thereof

A technology for reprogramming and purpose, applied in the field of biomedicine, can solve problems such as poor prognosis and recurrence

Inactive Publication Date: 2018-08-31
SHENZHEN SANQI BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

GBM has a very poor prognosis and usually relapses despite multiple modalities of treatment including surgery, radiation and chemotherapy

Method used

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  • Method for reprogramming cancer cells into non-cancer cells in vivo and application thereof
  • Method for reprogramming cancer cells into non-cancer cells in vivo and application thereof
  • Method for reprogramming cancer cells into non-cancer cells in vivo and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0116] Example 1: Screening of a library of protein kinase inhibitors against reprogrammed GBM cells

[0117] Because many protein kinases are known to be involved in aging and proliferation processes and thus have important functions in cancer cell reprogramming, a protein kinase inhibitor library (Calbiochem) containing 355 inhibitors was screened to identify potential inhibitors capable of reprogramming cancer cells. candidate compound.

[0118] Screening is performed by culturing cancer cells, in particular GBM cell lines, in induction media in combination with candidate protein kinase inhibitors and monitoring changes in cell morphology. A candidate protein kinase inhibitor has the ability to reprogram and transform cancer cells into normal cells when detectable morphological changes in cultured cancer cells are observed.

[0119] Materials used for screening are described in detail below.

[0120] Material

[0121] Cells: GBM cell lines U138, U118, U87, GM139 and GM97...

Embodiment 2

[0152] Example 2: Characterization of neurons generated by transformation of GBM cells with a combination of P529 and Y27632

[0153] Using the same method as in Example 1, the transformation efficiency using the combination of P529 and Y27632 was tested and the characteristics of the neuronal products transformed from GBM cells were verified ( Figure 4 ).

[0154] It was observed that in 1-2 weeks, 70%-85% of GBM cells were induced to become neuron-like cells and become iN cells ( Figure 4 A). These iN cells possess the morphology of awakened mature neurons, and the expression of neuronal markers including Tuj1, synapsin, MAP2, vGluT1, GABA and TBR1 ( Figure 4 B). After three weeks of induction, whole-cell voltage-clamp recordings at iNs revealed that 70% of iNs had functional voltage-dependent sodium and potassium currents and were capable of firing multiple action potentials ( Figure 4 C-E). These data suggest that iNs are functional neurons.

Embodiment 3

[0155] Example 3: Treatment of normal neurons and astrocytes with protein kinase inhibitors

[0156] Following the same procedure described in Example 1, mTOR-ROCK inhibitor (P+Y) treatment was also tested on normal neurons and astrocytes to assess whether the treatment had any inducing effect on normal cells. Primary mouse neurons / astrocytes were prepared for testing. Culture properties, neural markers (including MAP2, Prominin, GFAP and S100) and electrophysiological characterization were assessed compared to no-treatment controls (data not shown). found that mTOR‐ROCK treatment did not affect normal neuronal or astrocyte properties. Thus, the reprogramming conditions described in this disclosure are cancer cell specific.

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PUM

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Abstract

The invention relates to the field of biological medicine, in particular to a method for reprogramming cancer cells into non-cancer cells. The invention particularly provides a mixture (cocktail) andmethod for reprogramming cancer cells into non-cancer cells. In the method, the reprogramming mixture is applied to a tumor site and used for directly reprogramming malignant cells into non-malignantcells, more particularly, a packaged (encapsulated) reprogramming mixture is applied to a tumor site in a test person, particularly, is applied to glioblastoma multiforme (GBM) so that the GBM can beinduced to become non-malignant nerve cells and / or glial cells. The invention also relates to a method for preparing the mixture, such as, a method for preparing the reprogramming mixture containing one ore more protein kinase inhibitors.

Description

field of invention [0001] The invention relates to the field of biomedicine, in particular to reprogramming cancer cells into non-cancer cells. In particular, the application provides cocktails and methods for reprogramming cancer cells to non-cancer cells. The reprogramming cocktails of the present application include chemical or biological agents, such as small molecules, that are capable of inducing, effectuating or promoting the reprogramming of cancer cells to non-cancer cells. The methods of the present application involve administering the reprogramming mixture to a tumor site for direct reprogramming of malignant tumor cells into non-malignant cells. More specifically, the present disclosure relates to methods comprising administering an encapsulated reprogramming mixture to a tumor site in a subject, particularly glioblastoma (GBM), to induce GBM to become a non-malignant neuronal cells and / or glial cells. The present disclosure also relates to methods of making su...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61P35/00
CPCA61K45/06A61K9/0024
Inventor 鲁晓华杨佳银周敏刘雨晴闫玉波
Owner SHENZHEN SANQI BIOTECH
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