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Treatment of cancer by manipulation of commensal microflora

a commensal microflora and cancer technology, applied in the direction of antibacterial agents, drug compositions, antibody medical ingredients, etc., can solve the problems that the mechanisms that govern the presence or absence of this phenotype have not been well understood, and achieve the effects of inhibiting the growth or spread of cancer, enhancing immune response, and inhibiting immune evasion

Inactive Publication Date: 2019-06-20
UNIVERSITY OF CHICAGO
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent is about how to treat or prevent cancer in a person by changing the levels of bacteria in their gut. This change can help the person's immune system fight the cancer, stop the cancer from spreading, and even make treatments more effective. The bacteria that can be targeted include several genera of bacteria such as Adlercreutzia, Oscillopira, Mollicutes, Butyrivibrio, Bacteroides, Clostridium, Fusobacterium, Eubacterium, Ruminococcus, Peptococcus, Peptostreptococcus, Bifidobacterium, Rikenella, Alistipes, Marinilabilia, Anaerostipes, Escherichia, and Lactobacillus.

Problems solved by technology

Despite the functional and clinical importance of this T cell-inflamed tumor microenvironment, the mechanisms that govern the presence or absence of this phenotype have not been well understood.

Method used

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  • Treatment of cancer by manipulation of commensal microflora
  • Treatment of cancer by manipulation of commensal microflora
  • Treatment of cancer by manipulation of commensal microflora

Examples

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Materials and Methods

[0132]Animals and Tumor Model:

[0133]C57BL / 6 mice were obtained from Jackson laboratory or Taconic farms. 6-8-week-old female mice were used. The C57BL / 6-derived melanoma cell line B16.F10.SIY (referred to herein as B16.SIY) was generated (Blank et al. Cancer research 64, 1140-1145 (2004); herein incorporated by reference in its entirety). For tumor growth experiments, mice were injected subcutaneously with 1×106 B16.SIY tumor cells. Tumor size was measured twice a week until endpoint and tumor volume was determined as length×width2×0.5. For B16 parental tumor model experiments, mice were injected subcutaneously with 1×106 B16.F10 tumor cells. For bladder cancer model experiments, mice were injected subcutaneously with 2×106 MB49 cells. All experimental animal procedures were approved by the University of Chicago Animal Care and Use Committee (IACUC).

[0134]IFN-γ ELISPOT and SIY Pentamer Analyses:

[0135]Elispot plates (Millipore, MAIP S4510) were coated with purifi...

example 2

Results

[0148]Experiments were conducted during development of embodiments of the present invention to test whether differences in the specific composition of the normal microbiota influence the immune response to a growing tumor in vivo. Subcutaneous B16.SIY melanoma growth was observed in genetically similar C57BL / 6 mice derived from two different mouse facilities, Jackson Laboratory (JAX) and Taconic Farms (TAC), which have been shown to differ in their commensal microbes (Ivanov et al. Cell 139, 485-498 (2009); herein incorporated by reference in its entirety). It was found that JAX and TAC mice exhibited significant differences in B16.SIY melanoma growth rate, with tumors growing more aggressively in TAC mice (FIG. 1A). To evaluate whether this difference was immune-mediated, tumor antigen-specific T cell responses, as well as T cell accumulation in the tumor microenvironment, were assessed. In fact, tumor-specific T cell responses were significantly higher in JAX mice (FIGS. 1B...

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Abstract

Provided herein are methods of treatment and / or prevention of cancer by manipulation of commensal microflora. In particular, the amount, identity, presence, and / or ratio of microflora (e.g., gut microflora) in a subject is manipulated to facilitate one or more co-treatments.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]The present application is a continuation of U.S. patent application Ser. No. 15 / 718,735, filed Sep. 28, 2017, which is a continuation of U.S. patent application Ser. No. 15 / 170,284, filed Jun. 1, 2016, now U.S. Pat. No. 9,855,302, which claims the priority benefit of U.S. Provisional Patent Application 62 / 169,112, filed Jun. 1, 2015, and U.S. Provisional Patent Application 62 / 248,741, filed Oct. 30, 2015, each of which is incorporated by reference in its entirety.FIELD[0002]Provided herein are methods of treatment and / or prevention of cancer by manipulation of commensal microflora. In particular, the amount, identity, presence, and / or ratio of microflora (e.g., gut microflora) in a subject is manipulated to facilitate one or more co-treatments.BACKGROUND[0003]Harnessing the host immune system constitutes a promising approach for the treatment of cancer because of its potential to specifically target tumor cells while limiting harm to nor...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K35/741A61K39/395A61K35/742C07K16/28A61K45/06A61K35/747A61K35/745
CPCA61K35/741A61K39/39558A61K35/742C07K16/2827A61K45/06A61K35/747A61K35/745A61K2039/505C07K2317/76A61P31/04A61P35/00A61P35/02A61P43/00Y02A50/30A61K2300/00A61K9/0019A23L33/135A61K9/0053A23V2002/00A23V2200/308A23V2400/51
Inventor GAJEWSKI, THOMAS F.SIVAN, AYELETCORRALES, LETICIA
Owner UNIVERSITY OF CHICAGO
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