WO2005039491A3 - Certain improved combination bacteriolytic therapy for the treatment of tumors - Google Patents

Certain improved combination bacteriolytic therapy for the treatment of tumors Download PDF

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Publication number
WO2005039491A3
WO2005039491A3 PCT/US2004/034624 US2004034624W WO2005039491A3 WO 2005039491 A3 WO2005039491 A3 WO 2005039491A3 US 2004034624 W US2004034624 W US 2004034624W WO 2005039491 A3 WO2005039491 A3 WO 2005039491A3
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WO
WIPO (PCT)
Prior art keywords
tumors
microtubule
spores
agents
found
Prior art date
Application number
PCT/US2004/034624
Other languages
French (fr)
Other versions
WO2005039491A2 (en
WO2005039491A9 (en
Inventor
Long Dang
Chetan Bettegowda
Kenneth W Kinzler
Bert Vogelstein
Original Assignee
Univ Johns Hopkins
Long Dang
Chetan Bettegowda
Kenneth W Kinzler
Bert Vogelstein
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Univ Johns Hopkins, Long Dang, Chetan Bettegowda, Kenneth W Kinzler, Bert Vogelstein filed Critical Univ Johns Hopkins
Publication of WO2005039491A2 publication Critical patent/WO2005039491A2/en
Publication of WO2005039491A9 publication Critical patent/WO2005039491A9/en
Publication of WO2005039491A3 publication Critical patent/WO2005039491A3/en

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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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/06—Tripeptides

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Zoology (AREA)
  • Molecular Biology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Current approaches for treating cancer are limited, in part, by the inability of drugs to affect the poorly vascularized regions of tumors. We have found that spores of anaerobic bacteria in combination with agents which interact with microtubules can cause the destruction of both the vascular and avascular compartments of tumors. Two classes of microtubule inhibitors were found to exert markedly different effects. Some agents that inhibited microtubule synthesis such as HTI-286 and vinorelbine, caused rapid, massive hemorrhagic necrosis when used in combination with spores. In contrast, agents that stabilized microtubules, such as the taxanes docetaxel and MAC-321, resulted in slow tumor regressions that killed most neoplastic cells. Remaining cells in the poorly perfused regions of tumors could be eradicated by sporulated bacteria Mechanistic studies showed that the microtubule destabilizers, but not the microtubule stabilizers, radically reduced blood flow to tumors, thereby enlarging the hypoxic niche in which spores could germinate. A single intravenous injection of spores plus selected microtubule-interacting agents was able to cause regressions of several tumors in the absence of excessive toxicity.
PCT/US2004/034624 2003-10-22 2004-10-21 Certain improved combination bacteriolytic therapy for the treatment of tumors WO2005039491A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US51292203P 2003-10-22 2003-10-22
US60/512,922 2003-10-22

Publications (3)

Publication Number Publication Date
WO2005039491A2 WO2005039491A2 (en) 2005-05-06
WO2005039491A9 WO2005039491A9 (en) 2005-06-02
WO2005039491A3 true WO2005039491A3 (en) 2005-06-23

Family

ID=34520061

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2004/034624 WO2005039491A2 (en) 2003-10-22 2004-10-21 Certain improved combination bacteriolytic therapy for the treatment of tumors

Country Status (1)

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WO (1) WO2005039491A2 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005039492A2 (en) 2003-10-22 2005-05-06 The John Hopkins University Improved combination bacteriolytic therapy for the treatment of tumors

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030103987A1 (en) * 1996-02-02 2003-06-05 Christoph Von Eichel-Streiber Method of inactivation of ras subfamily proteins and agents therefor

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030103987A1 (en) * 1996-02-02 2003-06-05 Christoph Von Eichel-Streiber Method of inactivation of ras subfamily proteins and agents therefor

Also Published As

Publication number Publication date
WO2005039491A2 (en) 2005-05-06
WO2005039491A9 (en) 2005-06-02

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