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Anti-cancer oncolytic virus combination therapies and elite responder selection platforms

An oncolytic virus and selective technology, applied in viruses, anti-tumor drugs, gene therapy, etc., can solve the problems of low remission rate of anti-cancer therapy and lack of anti-tumor immunity in patients

Active Publication Date: 2018-11-06
胡敏杰 +3
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Another possible reason is that a large proportion of patients lack pre-prepared antitumor immunity, which leads to the low response rate of most systemic anticancer therapies

Method used

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  • Anti-cancer oncolytic virus combination therapies and elite responder selection platforms
  • Anti-cancer oncolytic virus combination therapies and elite responder selection platforms
  • Anti-cancer oncolytic virus combination therapies and elite responder selection platforms

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Example 1 – Gut microbiome experiments

[0058] A. Isolation of microbial strains

[0059] Isolation and Purification of Prajna's Microorganism Strains

[0060] Purification of specific strains by isolation of single bacterial colonies from bacterial cultures. The starting probiotic material containing several strains was serially diluted and cultured on solid agar plates. These plates contain well-separated colonies from which individual colonies are picked, each representing a single strain. Each picked colony was streaked onto a fresh plate and incubated at 37°C for 24-72 hours (depending on the strain) to allow new single colonies to form. This process is repeated several times to ensure that the bacteria within the colony are derived from a single clone. The final colonies were used to amplify selected strains.

[0061] B. Microorganism culture

[0062] Device Setup and Configuration

[0063] To start the anaerobic culture, fill the culture chamber of ...

Embodiment 2

[0097] Example 2 - Preparation of Oncolytic Viruses for Animal Injection

[0098] A. Adenocarcinoma human alveolar basal epithelial cell line A549 culture

[0099] Thaw A549 cells

[0100] By adding 2x 10 6 Frozen vials of cells / ml were transferred from the liquid nitrogen tank to a 37°C water bath to thaw A549 cells (Prajna code: C1; originally obtained from the BeNa Culture Collection, Cat# BNCC337696). Cell culture medium (10% FBS in DMEM) was warmed in a 37°C water bath. Thoroughly wipe the surface of the vial with 75% alcohol. The vial was opened in a cell culture hood and transferred to a 1.5 ml sterile tube with a P1000 pipette. Slowly add 10 ml of pre-warmed cell culture medium and centrifuge at 230 xg for 5 minutes at room temperature (RT). Pour off supernatant and resuspend cells in cell culture medium. cells at 0.7-2 x 10 6 Cell density per bottle was seeded to 75cm 2 flasks and placed in a 37°C cell culture incubator to allow cell growth. The culture m...

Embodiment 3

[0117] Example 3 – Eliminate the influence of gut microbes on tumor growth

[0118] To assess the suppressive function of the gut microbiota on tumor growth, an assay was developed showing that Bifidobacterium abundance was associated with slower tumor progression. C57BL / 6 mice were divided into two groups: T0: not treated with antibiotics; T1: treated with antibiotics. Mice in both groups were housed in our SPF facility for 4 days, treated with or without antibiotics for 2 weeks, and then inoculated subcutaneously with 10E6 B16-F10 cells. Tumors were measured daily starting from day 10 after inoculation. Fecal pellets were collected two weeks after B16 inoculation. The data showed that tumors on T1 mice generally grew faster than most T0 mice ( figure 1 ). This suggests that elimination of gut microbes enhances tumor growth, and further implies that microbes can suppress tumor progression.

[0119] Evaluation of different microbial genera using high-throughput 16S rRNA...

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Abstract

Therapeutic methods for administering gut microbiota and oncolytic viruses to a subject are provided. The gut microbiota serve to pre-condition, the subject's immune system to antitumor responses andaugments anticancer activity of the oncolytic vims. Combinations of the gut. microbiota and viruses and uses thereof for treating and preventing cancer are provided. The present disclosure also provides methods for building elite responder selection platforms through hierarchical clustering analysis of genomic profiles for human gut microbiome.

Description

[0001] related application [0002] This application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Application Serial No. 62 / 390,395, filed March 28, 2016. The content of this application is incorporated herein by reference in its entirety. technical field [0003] The present disclosure provides methods for administering gut microbiota and oncolytic viruses to a subject. Combinations of viruses and gut microbiota and their use for the treatment and prevention of cancer are also provided. Background technique [0004] Cancer is a class of diseases characterized by the uncontrolled growth of malignant cells. There are more than one hundred types of cancer affecting a large portion of the population, accounting for approximately 13% of all deaths. In 2012, more than 8.2 million people died of cancer worldwide, and this number is expected to soar to 13 million by 2030. The number of new cancer cases diagnosed worldwide in 2012 was 14.1 million, 58% of which we...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/12A61K39/285A61K48/00A01N63/00A61K45/00
CPCA61K39/39A61K2039/55594C12N7/00A61K45/06A61K35/745A61P35/00C12N2710/24021C12N2710/24032C12N2710/24121C12N2710/24132A61K35/768A61K35/741
Inventor 胡敏杰李禹刘晓玲R·胡
Owner 胡敏杰
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