Title:
COMBINATION THERAPY USING INHIBITORS OF HUMAN GROWTH AND DIFFERENTIATION FACTOR 15 (GDF-15) AND IMMUNE CHECKPOINT BLOCKERS
Document Type and Number:
WIPO Patent Application WO/2017/055613
Kind Code:
A3
Abstract:
The present invention relates to uses of inhibitors of human Growth and Differentiation Factor 15 (GDF-15), and to combined uses of such inhibitors with immune checkpoint blockers, in the treatment of solid cancers.
Inventors:
WISCHHUSEN JÖRG (DE)
HAAKE MARKUS (DE)
DUMMER REINHARD (CH)
MEHLING MATTHIAS (CH)
SCHÄFER TINA (DE)
SELLE MARTINA (DE)
HAAKE MARKUS (DE)
DUMMER REINHARD (CH)
MEHLING MATTHIAS (CH)
SCHÄFER TINA (DE)
SELLE MARTINA (DE)
Application Number:
PCT/EP2016/073520
Publication Date:
July 06, 2017
Filing Date:
September 30, 2016
Export Citation:
Assignee:
JULIUS-MAXIMILIANS-UNIVERSITÄT WÜRZBURG (DE)
International Classes:
A61K39/395; A61K31/00; C07K16/22; C07K16/28; G01N33/50; G01N33/574
Domestic Patent References:
| WO2015144855A1 | 2015-10-01 |
Other References:
TSUI KE-HUNG ET AL: "Growth differentiation factor-15: a p53- and demethylation-upregulating gene represses cell proliferation, invasion, and tumorigenesis in bladder carcinoma cells.", SCIENTIFIC REPORTS 2015, vol. 5, 7 August 2015 (2015-08-07), pages 12870, XP002765093, ISSN: 2045-2322
ARTZ ANNETTE ET AL: "GDF-15 inhibits integrin activation and mouse neutrophil recruitment through the ALK-5/TGF-[beta]RII heterodimer.", BLOOD 28 JUL 2016, vol. 128, no. 4, 28 July 2016 (2016-07-28), pages 529 - 541, XP002765094, ISSN: 1528-0020
NEUZILLET CINDY ET AL: "Targeting the TGF[beta] pathway for cancer therapy.", PHARMACOLOGY & THERAPEUTICS MAR 2015, vol. 147, March 2015 (2015-03-01), pages 22 - 31, XP002765095, ISSN: 1879-016X
HERBERTZ STEPHAN ET AL: "Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway.", DRUG DESIGN, DEVELOPMENT AND THERAPY 2015, vol. 9, 10 August 2015 (2015-08-10), pages 4479 - 4499, XP002765096, ISSN: 1177-8881
ADKINS CHRIS E ET AL: "A novel preclinical method to quantitatively evaluate early-stage metastatic events at the murine blood-brain barrier.", CANCER PREVENTION RESEARCH (PHILADELPHIA, PA.) JAN 2015, vol. 8, no. 1, January 2015 (2015-01-01), pages 68 - 76, XP002765097, ISSN: 1940-6215
YOON J -H ET AL: "Activin receptor-like kinase5 inhibition suppresses mouse melanoma by ubiquitin degradation of Smad4, thereby derepressing eomesodermin in cytotoxic T lymphocytes", EMBO MOLECULAR MEDICINE 2013 WILEY-BLACKWELL PUBLISHING LTD GBR, vol. 5, no. 11, November 2013 (2013-11-01), pages 1720 - 1739, XP002765098, ISSN: 1757-4676
S. L. TOPALIAN ET AL: "Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab", JOURNAL OF CLINICAL ONCOLOGY, vol. 32, no. 10, 3 March 2014 (2014-03-03), US, pages 1020 - 1030, XP055218601, ISSN: 0732-183X, DOI: 10.1200/JCO.2013.53.0105
SUCHARD SUZANNE J ET AL: "A monovalent anti-human CD28 domain antibody antagonist: preclinical efficacy and safety.", JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 1 NOV 2013, vol. 191, no. 9, 1 November 2013 (2013-11-01), pages 4599 - 4610, XP002765099, ISSN: 1550-6606
KEMPF TIBOR ET AL: "GDF-15 is an inhibitor of leukocyte integrin activation required for survival after myocardial infarction in mice.", NATURE MEDICINE MAY 2011, vol. 17, no. 5, May 2011 (2011-05-01), pages 581 - 588, XP002770366, ISSN: 1546-170X
ARTZ ANNETTE ET AL: "GDF-15 inhibits integrin activation and mouse neutrophil recruitment through the ALK-5/TGF-[beta]RII heterodimer.", BLOOD 28 JUL 2016, vol. 128, no. 4, 28 July 2016 (2016-07-28), pages 529 - 541, XP002765094, ISSN: 1528-0020
NEUZILLET CINDY ET AL: "Targeting the TGF[beta] pathway for cancer therapy.", PHARMACOLOGY & THERAPEUTICS MAR 2015, vol. 147, March 2015 (2015-03-01), pages 22 - 31, XP002765095, ISSN: 1879-016X
HERBERTZ STEPHAN ET AL: "Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway.", DRUG DESIGN, DEVELOPMENT AND THERAPY 2015, vol. 9, 10 August 2015 (2015-08-10), pages 4479 - 4499, XP002765096, ISSN: 1177-8881
ADKINS CHRIS E ET AL: "A novel preclinical method to quantitatively evaluate early-stage metastatic events at the murine blood-brain barrier.", CANCER PREVENTION RESEARCH (PHILADELPHIA, PA.) JAN 2015, vol. 8, no. 1, January 2015 (2015-01-01), pages 68 - 76, XP002765097, ISSN: 1940-6215
YOON J -H ET AL: "Activin receptor-like kinase5 inhibition suppresses mouse melanoma by ubiquitin degradation of Smad4, thereby derepressing eomesodermin in cytotoxic T lymphocytes", EMBO MOLECULAR MEDICINE 2013 WILEY-BLACKWELL PUBLISHING LTD GBR, vol. 5, no. 11, November 2013 (2013-11-01), pages 1720 - 1739, XP002765098, ISSN: 1757-4676
S. L. TOPALIAN ET AL: "Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab", JOURNAL OF CLINICAL ONCOLOGY, vol. 32, no. 10, 3 March 2014 (2014-03-03), US, pages 1020 - 1030, XP055218601, ISSN: 0732-183X, DOI: 10.1200/JCO.2013.53.0105
SUCHARD SUZANNE J ET AL: "A monovalent anti-human CD28 domain antibody antagonist: preclinical efficacy and safety.", JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 1 NOV 2013, vol. 191, no. 9, 1 November 2013 (2013-11-01), pages 4599 - 4610, XP002765099, ISSN: 1550-6606
KEMPF TIBOR ET AL: "GDF-15 is an inhibitor of leukocyte integrin activation required for survival after myocardial infarction in mice.", NATURE MEDICINE MAY 2011, vol. 17, no. 5, May 2011 (2011-05-01), pages 581 - 588, XP002770366, ISSN: 1546-170X
Attorney, Agent or Firm:
POLZ, Leo et al. (DE)
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