US20140079637A1 - Methods and compositions for improving antiangiogenic therapy with anti-integrins - Google Patents

Methods and compositions for improving antiangiogenic therapy with anti-integrins Download PDF

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US20140079637A1
US20140079637A1 US14/006,669 US201214006669A US2014079637A1 US 20140079637 A1 US20140079637 A1 US 20140079637A1 US 201214006669 A US201214006669 A US 201214006669A US 2014079637 A1 US2014079637 A1 US 2014079637A1
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integrin
agent
beta
antibody
tumor
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Warren Shawn Carbonell
Manish Kumar Aghi
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University of California San Diego UCSD
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University of California San Diego UCSD
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Assigned to THE REGENTS OF THE UNIVERSITY OF CALIFORNIA reassignment THE REGENTS OF THE UNIVERSITY OF CALIFORNIA ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: AGHI, MANISH KUMAR, CARBONELL, WARREN SHAWN
Assigned to THE REGENTS OF THE UNIVERSITY OF CALIFORNIA reassignment THE REGENTS OF THE UNIVERSITY OF CALIFORNIA ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: AGHI, MANISH KUMAR, CARBONELL, WARREN SHAWN
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • 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
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2839—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the integrin superfamily
    • C07K16/2842—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the integrin superfamily against integrin beta1-subunit-containing molecules, e.g. CD29, CD49
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A61K2039/507—Comprising a combination of two or more separate antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • 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
    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/15011—Lentivirus, not HIV, e.g. FIV, SIV
    • C12N2740/15041—Use of virus, viral particle or viral elements as a vector
    • C12N2740/15043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector

Definitions

  • the present invention comprises, in general, pharmaceutical compositions for inhibiting tumor cell growth, comprising: a first agent which is an inhibitor of VEGF activity, such as VEGF signaling and/or binding to the VEGF receptor; and a second agent which blocks beta-1 integrin.
  • the blocking of beta-1 integrin can be blocking of cell attachment, blocking of beta-integrin intracellular signaling that occurs after cell attachment, or both.
  • the agents used are compositions of matter, such as peptides or small molecules. They may be antibodies or antibody-like molecules. The combination of agents has a synergistic effect, i.e. is more effective than either agent separately.
  • the agents may be in a single composition or a matched pair of compositions.
  • FIG. 8 is a bar graph showing expression of annexin and Ki67 apoptosis markers at different concentrations of AIIB2 in an antiangiogenesis resistant glioblastoma cell line.
  • FIG. 12 is a bar graph showing cell growth over time of GBM cells subjected to hypoxia for 2 days followed by growth at normoxia. Cells were given IgG (control) and different concentrations of AIIB2.
  • FIG. 13 is a line graph showing tumor growth over time for U87MG glioma tumors measured biweekly with control IgG (10 mg/kg) (diamonds), bevacizumab (10 mg/kg) (squares), or low-dose alternating combination therapy of bevacizumab (1 mg/kg) and AIIB2 (1 mg/kg) (circles).
  • VEGF refers to vascular endothelial growth factor, also referred to as vasoendothelial growth factor, having an exemplary amino acid sequence at Genbank Accession Number AAA35789, described further at Leung, et al. “Vascular endothelial growth factor is a secreted angiogenic mitogen,” Science 246 (4935), 1306-1309 (1989). VEGF is a dimeric, disulfide-linked 46-kDa glycoprotein related to Platelet-Derived Growth Factor (“PDGF”).
  • PDGF Platelet-Derived Growth Factor
  • VEGFR-I also known as flt-1
  • VEGFR-2 also known as KDR3
  • VEGFR-3 VEGF receptor
  • the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the hypervariable loops correspond to those of a non-human immunoglobulin and all or substantially all of the FRs are those of a human immunoglobulin sequence.
  • the humanized antibody optionally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin.
  • Fc immunoglobulin constant region
  • antibody further includes various forms of modified or altered antibodies, such as various fragments such as an Fv fragment, an Fv fragment containing only the light and heavy chain variable regions, an Fv fragment linked by a disulfide bond (Brinkmann, et al. Proc. Natl. Acad. Sci. USA, 90: 547-551 (1993)), a Fab or (Fab)′2 fragment containing the variable regions and parts of the constant regions, a single-chain antibody and the like (Bird et al., Science 242: 424-426 (1988); Huston et al., Proc. Nat. Acad. Sci. USA 85: 5879-5883 (1988)).
  • fragments such as an Fv fragment, an Fv fragment containing only the light and heavy chain variable regions, an Fv fragment linked by a disulfide bond (Brinkmann, et al. Proc. Natl. Acad. Sci. USA, 90: 547-551 (1993)
  • Fab or (Fab)′2 fragment
  • tumors and metastases may be deprived of an adequate blood supply resulting in tumor cell growth arrest and possibly regression, including tumor cell death.
  • the methods have a variety of uses in scientific research and health care wherein vascularization is a contributing factor in disease processes, especially cancer.
  • enhancement of vascularization for repair or replacement of tissue may be achieved by potentiating both angiogenesis and adhesive vessel co-option simultaneously or sequentially.
  • anti-beta-1 compositions can be a monotherapy for 3L GBM who have failed Bevacizmab.
  • vascular niche a niche for insulin gene expression and beta cell proliferation.
  • vascular mural cells require the ⁇ 1 integrin subunit for proper adhesion to vessels and for maintaining vessel stability.
  • carcinoma cells appear to hijack the brain's VBM for essential functions during brain metastasis.
  • inhibiting angiogenesis in circumscribed, well-established CNS melanoma metastases causes reversion to growth by vascular co-option. This suggests a continuum for vessel utilization by tumor cells which may represent a viable target for therapeutic exploitation.
  • ⁇ 1 integrins In addition to the apoptotic mechanism described in vitro, inhibition of vascular co-option may have also attenuated growth.
  • tumors were analyzed in the MMTV/PyMT transgenic model of breast cancer.
  • Conditional deletion of ⁇ 1 integrin after induction of tumorigenesis resulted in impairment of FAK phosphorylation and proliferation consistent with a reliance on anchorage-dependent signaling for tumor growth.
  • Single chain recombinant antibodies may also be used, as described, for example in U.S. Pat. No. 5,840,300 to Williams et al, entitled “Methods and compositions comprising single chain recombinant antibodies,” hereby incorporated by reference for purposes of describing methods useful in the preparation of such compositions.
  • Kappa, heavy, and lambda immunoglobulin chains are amplified separately and are subsequently combined as single chains, using recombinant PCR, i.e., the splicing by overlap extension (SOE) PCR method, wherein the single chains comprise a heavy chain plus a kappa chain or a heavy chain plus a lambda chain.
  • SOE overlap extension
  • KDR-bp KDR-binding protein
  • Lys49PLA2 catalytically inactive PLA2 homologue
  • RNAi lentivirus The preparation of competent virus from DNA vectors involves packaging the construct into a cell line.
  • Packaging an RNAi lentivirus is essentially the same as packaging a lentivirus carrying a cDNA.
  • DNA vectors are transiently transfected into a packaging cell line-such as human 293 cells, and after 2-3 days the supernatant will contain the virus.
  • Spheroidal tumor cell growth in culture is a surrogate for stem-like phenotype and can be promoted/enriched by stressors such as hypoxia and acid pH.
  • Knockdown of beta1 in both a classic glioma cell line (U87MG) and the BRG3 bevacizumab resistant line significantly impaired spheroid formation (data not shown)
  • AIIB2 also inhibited spheroidal growth of U87MG glioma cells induced by 48 hours of hypoxia (data not shown).
  • beta1 integrin In addition to impairment of spheroidal growth, inhibition of beta1 integrin promoted reversal of EMT as demonstrated by a significant increase in tumor cell area and a 50% decrease in the mesenchymal receptor c-met (data not shown).
  • beta1 integrin may inhibit growth of tumors by 1) preventing vessel co-option and perivascular invasion (or invasion upon any classical ECM substrate), 2) reducing viability of tumor cells after insults such as IR and hypoxia possibly by promoting apoptosis, 3) directly inhibiting tumor cell proliferation, 4) directly inhibiting angiogenesis by targeting proliferating and migrating endothelial cells and 5) reversing the aggressive stem-like phenotype including epithelial to mesenchymal transition (EMT).
  • EMT epithelial to mesenchymal transition

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  • General Health & Medical Sciences (AREA)
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  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103561761A (zh) * 2011-03-23 2014-02-05 加利福尼亚大学董事会 用于使用抗-整合素改善抗血管生成疗法的方法和组合物
WO2014105910A1 (en) * 2012-12-26 2014-07-03 Oncosynergy, Inc. ANTI- INTEGRIN β1 ANTIBODY COMPOSITIONS AND METHODS OF USE THEREOF
EP3067698A1 (en) 2015-03-11 2016-09-14 Institut d'Investigació Biomèdica de Bellvitge (IDIBELL) Pd-ecgf as biomarker of cancer
EP3067369A1 (en) 2015-03-11 2016-09-14 Institut d'Investigació Biomèdica de Bellvitge (IDIBELL) Methods and compositions for the treatment of anti-angiogenic resistant cancer
WO2017032856A2 (en) 2015-08-25 2017-03-02 Histide Ag Compounds for inducing tissue formation and uses thereof
KR20180050744A (ko) * 2015-09-17 2018-05-23 히스티드 아게 신생물성 세포를 비-신생물성 세포로 전환시키기 위한 약제학적 회합물 및 이것의 용도
WO2017046229A1 (en) * 2015-09-17 2017-03-23 Histide Ag Pharmaceutical association of growth factor receptor agonist and adhesion protein inhibitor for converting a neoplastic cell into a non-neoplastic cell and uses thereof
HUE057153T2 (hu) * 2015-09-17 2022-04-28 Histide Ag Neoplasztikus sejt nem neoplasztikus sejtté alakításához használt gyógyszerészeti együttes, mely egy növekedésifaktor-receptor agonistából és egy adhéziós fehérjeinhibitorból áll, és ezek felhasználása
WO2020145669A1 (ko) * 2019-01-10 2020-07-16 에스지메디칼 주식회사 항 베타 1 인테그린 인간화 항체 및 이를 포함하는 암치료용 약학 조성물

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6252043B1 (en) * 1989-04-28 2001-06-26 Biogen, Inc. Vascular cell adhesion molecule (VCAM) polypeptides
WO2008060645A2 (en) * 2006-03-21 2008-05-22 Genentech, Inc. Combinatorial therapy involving alpha5beta1 antagonists
US20090041767A1 (en) * 2007-07-27 2009-02-12 Vanitha Ramakrishnan Pharmaceutical combinations
WO2010111254A1 (en) * 2009-03-25 2010-09-30 Genentech, Inc. Novel anti-alpha5beta1 antibodies and uses thereof

Family Cites Families (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
US6033665A (en) 1989-09-27 2000-03-07 Elan Pharmaceuticals, Inc. Compositions and methods for modulating leukocyte adhesion to brain endothelial cells
US6165467A (en) 1991-07-20 2000-12-26 Yoshihide Hagiwara Stabilized human monoclonal antibody preparation
US5840300A (en) 1995-09-11 1998-11-24 Trustees Of The University Of Pennsylvania Methods and compositions comprising single chain recombinant antibodies
US5846536A (en) * 1996-10-04 1998-12-08 The Regents Of The University Of California Restoration of normal phenotype in cancer cells
US6596276B1 (en) 1997-09-30 2003-07-22 Beth Israel Deaconess Medical Center Method for inhibiting tumor angiogenesis in a living subject
WO1999058139A2 (en) * 1998-05-08 1999-11-18 The Regents Of The University Of California Methods for detecting and inhibiting angiogenesis
CA2359244C (en) 1999-01-13 2013-10-08 Bayer Corporation .omega.-carboxy aryl substituted diphenyl ureas as p38 kinase inhibitors
EP1140840B1 (en) 1999-01-13 2006-03-22 Bayer Pharmaceuticals Corp. -g(v)-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
US7928239B2 (en) 1999-01-13 2011-04-19 Bayer Healthcare Llc Inhibition of RAF kinase using quinolyl, isoquinolyl or pyridyl ureas
US6949245B1 (en) 1999-06-25 2005-09-27 Genentech, Inc. Humanized anti-ErbB2 antibodies and treatment with anti-ErbB2 antibodies
US6716410B1 (en) 1999-10-26 2004-04-06 The Regents Of The University Of California Reagents and methods for diagnosing, imaging and treating atherosclerotic disease
JP3789066B2 (ja) 1999-12-08 2006-06-21 三菱電機株式会社 液晶表示装置
US8725620B2 (en) 2000-07-10 2014-05-13 Nobuyoshi Morimoto System and method for negotiating improved terms for products and services being purchased through the internet
US6995162B2 (en) 2001-01-12 2006-02-07 Amgen Inc. Substituted alkylamine derivatives and methods of use
US6878714B2 (en) 2001-01-12 2005-04-12 Amgen Inc. Substituted alkylamine derivatives and methods of use
WO2002097038A2 (en) * 2001-05-25 2002-12-05 Human Genome Sciences, Inc. Chemokine beta-1 fusion proteins
JP4351043B2 (ja) 2001-07-09 2009-10-28 エラン ファーマシューティカルズ，インコーポレイテッド アミロイド毒性の阻害方法
US7307071B2 (en) 2001-12-04 2007-12-11 Onyx Pharmaceuticals, Inc RAF-MEK-ERK pathway inhibitors to treat cancer
UA84156C2 (ru) 2003-07-23 2008-09-25 Байер Фармасьютикалс Корпорейшн Фторозамещённая омега-карбоксиарилдифенилмочевина для лечения и профилактики болезней и состояний
TW200536851A (en) 2004-01-23 2005-11-16 Amgen Inc Compounds and methods of use
WO2005117976A2 (en) * 2004-06-03 2005-12-15 The Regent Of The University Of California Method of increasing radiation sensitivity by inhibition of beta one integrin
AU2006261920A1 (en) 2005-06-23 2007-01-04 Medimmune, Llc Antibody formulations having optimized aggregation and fragmentation profiles
AR059066A1 (es) 2006-01-27 2008-03-12 Amgen Inc Combinaciones del inhibidor de la angiopoyetina -2 (ang2) y el inhibidor del factor de crecimiento endotelial vascular (vegf)
JP4997432B2 (ja) 2006-02-10 2012-08-08 学校法人慶應義塾 神経幹細胞の増殖抑制剤
CN101448858B (zh) * 2006-03-21 2013-06-12 健泰科生物技术公司 牵涉α5β1拮抗剂的联合疗法
WO2008031064A1 (en) * 2006-09-07 2008-03-13 University Of South Florida Hyd1 peptides as anti-cancer agents
WO2009009114A2 (en) * 2007-07-12 2009-01-15 Oncomed Pharmaceuticals, Inc. Compositions and methods for treating and diagnosing cancer
EP2060287B1 (de) * 2007-11-14 2011-06-15 BrainLAB AG Medikamentenzuführungssystem für CED (Convection Enhanced Delivery)-Katheterinfusionen
CA2734863A1 (en) * 2008-08-20 2010-02-25 New York Blood Center, Inc. Regulation of integrin surface expression
EP2379596A1 (en) * 2008-12-23 2011-10-26 AstraZeneca AB Targeted binding agents directed to 5 1 and uses therefor
CN103561761A (zh) * 2011-03-23 2014-02-05 加利福尼亚大学董事会 用于使用抗-整合素改善抗血管生成疗法的方法和组合物
WO2014105910A1 (en) * 2012-12-26 2014-07-03 Oncosynergy, Inc. ANTI- INTEGRIN β1 ANTIBODY COMPOSITIONS AND METHODS OF USE THEREOF

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6252043B1 (en) * 1989-04-28 2001-06-26 Biogen, Inc. Vascular cell adhesion molecule (VCAM) polypeptides
WO2008060645A2 (en) * 2006-03-21 2008-05-22 Genentech, Inc. Combinatorial therapy involving alpha5beta1 antagonists
US20090220504A1 (en) * 2006-03-21 2009-09-03 Anan Chuntharapai Combinatorial therapy
US20090041767A1 (en) * 2007-07-27 2009-02-12 Vanitha Ramakrishnan Pharmaceutical combinations
WO2010111254A1 (en) * 2009-03-25 2010-09-30 Genentech, Inc. Novel anti-alpha5beta1 antibodies and uses thereof

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
Carnevale et al. Regulation of Postangiogenic Neovessel Survival by beta1 and beta3 Integrins in Collagen and Fibrin Matrices. J. Vasc Res. 2007; 44:40-50. *
Chekenya et al. The progenitor cell marker NG2/MPG promotes chemoresistance by activation of integrin-dependent PI3K/Akt signaling. Oncogene (2008) 27, 5182-5194 *
Chen, Tom T, Context-dependent VEGF signaling: molecular regulation of vascular patterning during angiogenesis. University of California, Los Angeles . Dissertation, 2009, 235 pages. *
Friedlander et al. Migration of Brain Tumor Cells on Extracellular Matrix Proteins in Vitro Correlates with Tumor Type and Grade and Involves αv, and ß1 Integrins. CANCERRESEARCH56. 1939-1947. April 15. 19961 *
Hemler et al. Structure of the integrin VLA-4 and its cell-cell and cell-matrix adhesion functions. (1990) Immunological Reviews 14:45-65. *
Park et al. beta1 Integrin Inhibition Dramatically Enhances Radiotherapy Efficacy in Human Breast Cancer Xenografts. Cancer Res. 2008 Jun 1; 68(11): 4398-4405. *
Tol et al. Chemotherapy, Bevacizumab, and Cetuximab in Metastatic Colorectal Cancer. N Engl J Med 2009;360:563-72. *
Yang et al. Embryonic mesodermal defects in 5 integrin-deficient mice. Development 119, 1093-1105 (1993) *

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CN103561761A (zh) 2014-02-05
US20180236073A1 (en) 2018-08-23
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AU2012230809B2 (en) 2017-06-29
US11185585B2 (en) 2021-11-30
EP2688585A4 (en) 2015-05-06
KR20140030153A (ko) 2014-03-11
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JP2014523398A (ja) 2014-09-11
EP2688585B1 (en) 2018-09-05

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