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WO2017074257A1 - Dérivés non viables de clostridium sporogenes utilisés comme agents thérapeutiques anti-cancéreux - Google Patents

Dérivés non viables de clostridium sporogenes utilisés comme agents thérapeutiques anti-cancéreux Download PDF

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Publication number
WO2017074257A1
WO2017074257A1 PCT/SG2016/050508 SG2016050508W WO2017074257A1 WO 2017074257 A1 WO2017074257 A1 WO 2017074257A1 SG 2016050508 W SG2016050508 W SG 2016050508W WO 2017074257 A1 WO2017074257 A1 WO 2017074257A1
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WIPO (PCT)
Prior art keywords
cell
bacterial
cancer
cells
derivative
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Ceased
Application number
PCT/SG2016/050508
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English (en)
Inventor
Swee Hin Teoh
Madhura Satish BHAVE
Ammar Mansoor HASSANBHAI
Padmaja ANAND
Qian Kathy LUO
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Nanyang Technological University
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Nanyang Technological University
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Publication of WO2017074257A1 publication Critical patent/WO2017074257A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/742—Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/164—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/4873—Cysteine endopeptidases (3.4.22), e.g. stem bromelain, papain, ficin, cathepsin H
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/52—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from bacteria or Archaea
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/22—Cysteine endopeptidases (3.4.22)
    • C12Y304/22008—Clostripain (3.4.22.8)

Definitions

  • RT involves the use of ionizing radiation to curb the growth of cancer cells by forming free-radical debris of DNA. Oxygen molecules react with the free-radical DNA debris to make the DNA damage permanent and bring about cell death. This makes the efficacy of RT heavily dependent on the presence of oxygen and thus, intra-tumoral hypoxia greatly curbs the effectiveness of RT in treating tumors 6 . Hypoxia also compromises on the efficacy of chemotherapy. There are various reasons for this. Firstly, these hypoxic tumor regions are located far away from the blood vessels, preventing the delivery of chemotherapeutic drugs to cells 7 8 .
  • Clostridium sporogenes a proteolytic species
  • Clostridium sporogenes a proteolytic species
  • Wild-type clostridial spores have been found to exert oncolytic effects on tumors 22 23
  • clostridial spores combined with other cancer therapies were found to have an enhanced anti-cancer effect 24 25
  • genetically modified clostridial species have also been used in Clostridium-directed enzyme prodrug therapy (CDEPT) 16 ' 20 ' 21 26 .
  • CDEPT Clostridium-directed enzyme prodrug therapy
  • nonviable bacterial derivatives or a composition comprising at least one bacterial protein.
  • the nonviable bacterial derivative or the composition can be efficiently used for the treatment of cancer. These therapeutic agents are non-infectious. In addition, they demonstrate significant inhibition of cancer growth in 3D cancer cell models.
  • the non-viable bacterial derivative is an inactivated Clostridium cell, preferably an inactivated Clostridium sporogenes cell.
  • disturbing the integrity of the extracellular matrix includes size regression of the extracellular matrix.
  • Clostridium sporogenes relates to a species of Gram- positive bacteria that belongs to the genus Clostridium. Like other strains of Clostridium, it is an anaerobic, rod-shaped bacterium that produces oval, subterminal endospores and is commonly found in soil. Unlike Clostridium botulinum, it does not produce the botulinum neurotoxins. In colonized animals, it has a mutualistic rather than pathogenic interaction with the host.
  • Oil refers to a cell, tissue or organism capable of expressing a protein of interest that naturally occurs in said cell, tissue or organism.
  • disturbing the integrity of the extracellular matrix includes size regression of the extracellular matrix.
  • the invention relates to a non-viable bacterial derivative, wherein the non-viable bacterial derivative comprises a heat inactivated Clostridium sporogenes cell.
  • 0.1 OD IB appears to stunt the spheroid growth, with the increase in the area of the spheroids being marginal at each time point (Fig. 5b). Over time, there is a significant difference in the area of the spheroids and at the end of 72 hours, the CT26 spheroids exposed to IB (3.25 x 10 5 ⁇ 2 ) are 25% smaller than the control spheroids (4.34 x 10 5 ⁇ 2 ) and the HCT116 spheroids exposed to IB (1.60 x 10 5 ⁇ 2 ) are 44% smaller than the control (2.85 x 10 5 ⁇ 2 ).

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Microbiology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Epidemiology (AREA)
  • Mycology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Virology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

L'invention concerne un dérivé bactérien non viable destiné à être utilisé comme médicament et une composition comprenant au moins une protéine bactérienne destinée à être utilisée comme médicament. La présente invention concerne également l'utilisation dudit dérivé bactérien et de ladite protéine dans le traitement du cancer et pour perturber l'intégrité de la matrice extracellulaire (MEC) d'une cellule. L'invention concerne en particulier une Clostridium sporogenes inactivée par la chaleur et une composition comprenant de la clostripaïne.
PCT/SG2016/050508 2015-10-26 2016-10-18 Dérivés non viables de clostridium sporogenes utilisés comme agents thérapeutiques anti-cancéreux Ceased WO2017074257A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SG10201508832Q 2015-10-26
SG10201508832Q 2015-10-26

Publications (1)

Publication Number Publication Date
WO2017074257A1 true WO2017074257A1 (fr) 2017-05-04

Family

ID=58631057

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/SG2016/050508 Ceased WO2017074257A1 (fr) 2015-10-26 2016-10-18 Dérivés non viables de clostridium sporogenes utilisés comme agents thérapeutiques anti-cancéreux

Country Status (1)

Country Link
WO (1) WO2017074257A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019070913A1 (fr) * 2017-10-03 2019-04-11 Seres Therapeutics, Inc. Manipulation du métabolisme de la tryptamine
CN115244069A (zh) * 2019-12-18 2022-10-25 埃克斯欧姆尼斯生物技术有限公司 遗传修饰的梭状杆菌菌株及其用途
US11666612B2 (en) 2013-03-15 2023-06-06 Seres Therapeutics, Inc Network-based microbial compositions and methods
WO2024201041A3 (fr) * 2023-03-27 2024-12-05 University Of Newcastle Upon Tyne Compositions probiotiques et postbiotiques, produits et leurs utilisations
US12214002B2 (en) 2017-10-30 2025-02-04 Seres Therapeutics, Inc. Compositions and methods for treating antibiotic resistance

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB970365A (en) * 1960-01-27 1964-09-23 Hoechst Ag Preparations for the treatment of tumours
WO2001034176A1 (fr) * 1999-10-28 2001-05-17 Immunolytics Inc. Methode et composition de traitement du cancer de la prostate
US20050244924A1 (en) * 2002-05-24 2005-11-03 Wagner Fred W Methods and constructs for high yield expression of clostripain
WO2005120560A1 (fr) * 2004-06-07 2005-12-22 Harold David Gunn Compositions bacteriennes pour le traitement d'un cancer
JP2009269836A (ja) * 2008-05-01 2009-11-19 Miyarisan Pharmaceutical Co Ltd 大腸癌細胞増殖抑制物質
US20110086018A1 (en) * 2005-10-03 2011-04-14 Biomedicure Proteinases destroy cancer tumor's solid structure and kill cancer cells locally
WO2013106510A2 (fr) * 2012-01-12 2013-07-18 Auxilium Pharmaceuticals, Inc. Enzymes de clostridium histolyticum et procédés pour les utiliser
EP2865748A1 (fr) * 2012-05-31 2015-04-29 Cristália Produtos Químicos Farmacêuticos LTDA. Milieu de culture pour bactéries du genre clostridium exempt de constituants d'origine animal et procédé de production d'un surnageant contenant une ou plusieurs protéases à activité collagénolytique et gélatinolytique

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB970365A (en) * 1960-01-27 1964-09-23 Hoechst Ag Preparations for the treatment of tumours
WO2001034176A1 (fr) * 1999-10-28 2001-05-17 Immunolytics Inc. Methode et composition de traitement du cancer de la prostate
US20050244924A1 (en) * 2002-05-24 2005-11-03 Wagner Fred W Methods and constructs for high yield expression of clostripain
WO2005120560A1 (fr) * 2004-06-07 2005-12-22 Harold David Gunn Compositions bacteriennes pour le traitement d'un cancer
US20110086018A1 (en) * 2005-10-03 2011-04-14 Biomedicure Proteinases destroy cancer tumor's solid structure and kill cancer cells locally
JP2009269836A (ja) * 2008-05-01 2009-11-19 Miyarisan Pharmaceutical Co Ltd 大腸癌細胞増殖抑制物質
WO2013106510A2 (fr) * 2012-01-12 2013-07-18 Auxilium Pharmaceuticals, Inc. Enzymes de clostridium histolyticum et procédés pour les utiliser
EP2865748A1 (fr) * 2012-05-31 2015-04-29 Cristália Produtos Químicos Farmacêuticos LTDA. Milieu de culture pour bactéries du genre clostridium exempt de constituants d'origine animal et procédé de production d'un surnageant contenant une ou plusieurs protéases à activité collagénolytique et gélatinolytique

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BHAVE, M.S. ET AL.: "Effect of Heat-Inactivated Clostridium sporogenes and Its Conditioned Media on 3-Dimensional Colorectal Cancer Cell Models.", SCI REP., vol. 5, 28 October 2015 (2015-10-28), pages 1 - 11, XP055379758, [retrieved on 20161228] *
CHEN, H.Y. ET AL.: "Antimetastatic activity induced by Clostridium butyricum and characterization of effector cells", ANTICANCER RES, vol. 13, no. 1, February 1993 (1993-02-01), pages 107 - 111, [retrieved on 20161228] *
SCHMIDT, W. ET AL.: "The tumour-Clostridium phenomenon: 50 years of developmental research (Review).", INT J ONCOL, vol. 29, no. 6, 1 December 2006 (2006-12-01), pages 1479 - 1492, XP055379751, [retrieved on 20161228] *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11666612B2 (en) 2013-03-15 2023-06-06 Seres Therapeutics, Inc Network-based microbial compositions and methods
WO2019070913A1 (fr) * 2017-10-03 2019-04-11 Seres Therapeutics, Inc. Manipulation du métabolisme de la tryptamine
US12214002B2 (en) 2017-10-30 2025-02-04 Seres Therapeutics, Inc. Compositions and methods for treating antibiotic resistance
CN115244069A (zh) * 2019-12-18 2022-10-25 埃克斯欧姆尼斯生物技术有限公司 遗传修饰的梭状杆菌菌株及其用途
WO2024201041A3 (fr) * 2023-03-27 2024-12-05 University Of Newcastle Upon Tyne Compositions probiotiques et postbiotiques, produits et leurs utilisations

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