WO2018236828A3 - Treatiing disease by modulating arginase 2 activity in regulatory t-cells - Google Patents

Treatiing disease by modulating arginase 2 activity in regulatory t-cells Download PDF

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Publication number
WO2018236828A3
WO2018236828A3 PCT/US2018/038225 US2018038225W WO2018236828A3 WO 2018236828 A3 WO2018236828 A3 WO 2018236828A3 US 2018038225 W US2018038225 W US 2018038225W WO 2018236828 A3 WO2018236828 A3 WO 2018236828A3
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WO
WIPO (PCT)
Prior art keywords
arg2
tregs
activity
regulatory
cells
Prior art date
Application number
PCT/US2018/038225
Other languages
French (fr)
Other versions
WO2018236828A2 (en
Inventor
Michael Rosenblum
Margaret LOWE
Original Assignee
The Regents Of The University Of California
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Publication date
Application filed by The Regents Of The University Of California filed Critical The Regents Of The University Of California
Publication of WO2018236828A2 publication Critical patent/WO2018236828A2/en
Publication of WO2018236828A3 publication Critical patent/WO2018236828A3/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/18—Sulfonamides
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
    • 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
    • A61K31/69—Boron compounds
    • 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)
    • A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Abstract

Arginase 2 (Arg2) is shown herein to control the suppressive activity of regulatory T-Cells (Tregs). Arg2 is deficient in the Tregs of tissues having autoimmune conditions, such as in the skin lesions of psoriasis. Autoimmune conditions may be treated by Arg2 agonists, increasing Treg expression of Arg2, or the administration of Tregs (such as skin-tropic Tregs in the case of epidermal autoimmune conditions) engineered to express Arg2. Further, Treg suppressive activity in cancer blunts the immune response against the tumor and reduces the efficacy of immunotherapy treatment. Cancer may be treated by administration of an Arg2 inhibitor or by administering Tregs (such as tumor-associated Tregs) engineered to have reduced Arg2 expression. Also provided are diagnostic kits and methods, wherein Treg suppressive capacity is assessed by measuring Arg2 activity.
PCT/US2018/038225 2017-06-19 2018-06-19 Treatiing disease by modulating arginase 2 activity in regulatory t-cells WO2018236828A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201762522084P 2017-06-19 2017-06-19
US62/522,084 2017-06-19

Publications (2)

Publication Number Publication Date
WO2018236828A2 WO2018236828A2 (en) 2018-12-27
WO2018236828A3 true WO2018236828A3 (en) 2019-02-07

Family

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Family Applications (1)

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PCT/US2018/038225 WO2018236828A2 (en) 2017-06-19 2018-06-19 Treatiing disease by modulating arginase 2 activity in regulatory t-cells

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WO (1) WO2018236828A2 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3774843B1 (en) 2018-03-29 2022-05-25 Molecure SA Dipeptide piperidine derivatives
CN110305857A (en) * 2019-05-22 2019-10-08 中国人民解放军第四军医大学 The method that mouse skin digests complex enzyme and separates skeptophylaxis cell Treg cell from mouse skin
CN110257353A (en) * 2019-05-22 2019-09-20 中国人民解放军第四军医大学 The method that application on human skin digests complex enzyme and separates skeptophylaxis cell Treg cell from people on a small quantity full pachydermia
GB201912030D0 (en) * 2019-08-21 2019-10-02 Cancer Research Tech Ltd Binding molecules

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017040670A1 (en) * 2015-09-01 2017-03-09 Ifm Therapeutics, Inc Immune cells having increased immunity or resistance to an immunosuppressive cytokine and use of the same

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017040670A1 (en) * 2015-09-01 2017-03-09 Ifm Therapeutics, Inc Immune cells having increased immunity or resistance to an immunosuppressive cytokine and use of the same

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
BLUESTONE, J. A. ET AL.: "The therapeutic potential of regulatory T cells for the treatment of autoimmune disease", EXPERT OPINION ON THERAPEUTIC TARGETS, vol. 19, no. 8, 2015, pages 1091 - 1103, XP055569196 *
BRON, L. ET AL.: "Prognostic value of arginase-II expression and regulatory T- cell infiltration in head and neck squamous cell carcinoma", INTERNATIONAL JOURNAL OF CANCER, vol. 132, 2013, pages E85 - E93, XP055569252 *
PACKER, H. ET AL.: "How to design gene disruption experiments using the Alt -R? CRISPR-Cas9 System", INTEGRATED DNA TECHNOLOGIES, 10 March 2016 (2016-03-10), pages 1 - 8, XP055569233, Retrieved from the Internet <URL:https://pdfs.semanticscholar.org/12cd/8dd9c4d3b7c1d3b45c94296691416f1f7148.pdf> *
PANDEY, D. ET AL.: "Transcriptional regulation of endothelial arginase 2 by histone deacetylase 2", ARTERIOSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY, vol. 34, 2014, pages 1556 - 1566, XP055569191 *
TIMOSENKO, E. ET AL.: "Modulation of cancer-specific immune responses by amino acid degrading enzymes", IMMUNOTHERAPY, vol. 9, no. 1, 2017, pages 83 - 97, XP055569187 *

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