Microorganisms programmed to produce immune modulators and Anti-cancer therapeutics in tumor cells

A technology of microorganisms and cells, applied in the direction of microorganisms, tumor necrosis factor, cytokines/lymphokines/interferons, etc., to achieve the effect of increasing the immune response in tumors

Pending Publication Date: 2020-03-24
SYNLOGIC OPERATING CO INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Therefore, effective cancer treatments exist that can target poorly vascularized hypoxic tumor regions, specifically target cancer cells, while minimally affecting normal tissues, and boost the immune system to fight tumors, including avoiding or reversing tumor immune tolerance. unmet needs

Method used

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  • Microorganisms programmed to produce immune modulators and Anti-cancer therapeutics in tumor cells
  • Microorganisms programmed to produce immune modulators and Anti-cancer therapeutics in tumor cells
  • Microorganisms programmed to produce immune modulators and Anti-cancer therapeutics in tumor cells

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[1543] Example 1 Anti-cancer molecules

[1544] The exemplary nucleic acid sequence used in the construction of the single-chain anti-CTLA-4 antibody is described in the international patent application PCT / US2017 / 013072 filed on January 11, 2017 and published as WO2017 / 123675, the entire content of which is incorporated herein by reference, For example, in Example 1. In some embodiments, the genetically engineered bacteria comprise a nucleic acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% homologous or comprising a DNA sequence The DNA sequence, the DNA sequence encoding and SEQ ID NO: 765, SEQ ID NO: 766, SEQ ID NO: 767, SEQ ID NO: 768, SEQ ID NO: 769, SEQ ID NO: 770, SEQ ID NO : 771, SEQ ID NO772, SEQ ID NO: 773, SEQ ID NO: 774, SEQ ID NO: 775 and / or SEQ ID NO: 776 at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least About 99% homologous polypeptide. In another...

Embodiment 2

[1546] Example 2. Tumor pharmacokinetics of E. coli Nissle

[1547] The tumor pharmacokinetics was measured and determined as described in the international patent application PCT / US2017 / 013072 published as WO2017 / 123675 filed on January 11, 2017, the entire contents of which are incorporated herein by reference, for example, Examples 58-61. The CT26 tumor model was used to determine the tumor pharmacokinetics of Nissle (1e7 and 1e8 cells / dose) within 7 days. The counts of bacteria in tumor tissues were similar at both doses. No bacteria were detected in the blood at any point in time.

[1548] The tumor pharmacokinetics of streptomycin-resistant Nissle and Nissle DOM mutant (Nissle deltaPAL::CmR) were compared in the CT26 tumor model. The counts of bacteria in tumor tissues were similar in both strains. No bacteria were detected in the blood. These results indicate that both wild-type and DOM mutant Nissle can survive in the tumor environment.

[1549] The CT26 tumor model was...

Embodiment 3A

[1551] Example 3A. LC-MS / MS quantification of metabolites

[1552] As described in the international patent application PCT / US2017 / 013072 published as WO2017 / 123675 filed on January 11, 2017, the bacterial supernatant and the adenosine, kynurenine, The quantification of tryptophan and arginine, the entire contents of which are incorporated herein by reference.

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Abstract

Genetically programmed microorganisms, such as bacteria or virus, pharmaceutical compositions thereof, and methods of modulating and treating cancers are disclosed.

Description

[0001] Related application [0002] This application requires U.S. provisional application number 62 / 443,634 filed on January 6, 2017; U.S. provisional application number 62 / 443,639 filed on January 6, 2017; PCT application number PCT / US2017 / filed on January 11, 2017 013072; US provisional application number 62 / 531,784 filed on July 12, 2017; US provisional application number 62 / 543,322 filed on August 9, 2017; US provisional application number 62 / 552,319 filed on August 30, 2017; Priority of U.S. Provisional Application No. 62 / 592,317 filed on November 29, 2017; and U.S. Provisional Application No. 62 / 607,210 filed on December 18, 2017; the entire contents of which are each expressly incorporated herein by reference. [0003] Sequence Listing [0004] This application contains a sequence listing, which has been electronically submitted in ASCII format, and its entire contents are incorporated herein by reference. The ASCII copy was created on January 4, 2018, the name is 126046_2...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K35/74C12N15/70C12N15/74A61K33/243
CPCA61K35/74C07K16/00C12N9/00A61K38/00C07K14/521C07K14/525C07K14/53C07K14/5434C07K14/5443C07K14/57C07K14/70575C07K14/70596C07K16/2803C12Y302/01035C12N9/14C12N9/2408C07K2319/00C07K2319/21C12Y307/01003C07K16/2818A61K2039/505C07K2317/622A61K31/4745A61K31/4995A61K31/506A61K31/513A61K31/555A61K31/7068A61K35/745A61K39/395A61K39/3955A61K45/06A61K2039/507C07K14/535C07K2317/14C12N9/2474A61P35/00A61K33/243C07K2319/02Y02A50/30A61K2300/00A61K33/24C12N15/62C12N15/74C12N2840/002C12Y302/01003
Inventor D·法尔布J·W·科图拉V·M·伊莎贝拉P·F·米勒S·马奇纳尼S·萨哈A·费舍尔Y·米利特李宁J·M·罗拉
Owner SYNLOGIC OPERATING CO INC
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