[go: up one dir, main page]

WO2017158393A1 - Méthodes de traitement d'une maladie du greffon contre l'hôte - Google Patents

Méthodes de traitement d'une maladie du greffon contre l'hôte Download PDF

Info

Publication number
WO2017158393A1
WO2017158393A1 PCT/IB2016/000440 IB2016000440W WO2017158393A1 WO 2017158393 A1 WO2017158393 A1 WO 2017158393A1 IB 2016000440 W IB2016000440 W IB 2016000440W WO 2017158393 A1 WO2017158393 A1 WO 2017158393A1
Authority
WO
WIPO (PCT)
Prior art keywords
gvhd
subject
agent
vedolizumab
intestinal
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/IB2016/000440
Other languages
English (en)
Inventor
Yngvar FLOISAND
Knut LUNDIN
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Oslo Universitetssykehus hf
Original Assignee
Oslo Universitetssykehus hf
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 Oslo Universitetssykehus hf filed Critical Oslo Universitetssykehus hf
Priority to PCT/IB2016/000440 priority Critical patent/WO2017158393A1/fr
Publication of WO2017158393A1 publication Critical patent/WO2017158393A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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
    • A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
    • 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
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • 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
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Definitions

  • the present invention relates to methods for the treatment of graft-versus-host disease (GVHD).
  • GVHD graft-versus-host disease
  • the present invention relates to methods of treating GVHD with agents that target integrin ⁇ 4 ⁇ 7.
  • Acute graft-versus-host disesase occurs in up to 50 % of patients after allogeneic stem cell transplantation.
  • Grade III-IV GvHD is associated with poor outcome, 70 - 90 % mortality (1, 2).
  • Severe intestinal involvement is particularly difficult to treat and often leads to prolonged illness before death occurs.
  • Treatment of steroid refractory or steroid dependent acute GvHD is notoriously difficult.
  • Second and third line treatments are not well documented and show erratic responses.
  • all treatment modalities of steroid refractory acute GvHD imply intensifying systemic immunosuppression with the risk of excess mortality due to infectious complications.
  • the present invention relates to methods for the treatment of graft-versus-host disease
  • the present invention relates to methods of treating GVHD with agents that target integrin ⁇ 4 ⁇ 7.
  • the present invention provides the use of an agent that inhibits one or more biological activities of integrin ⁇ 4 ⁇ 7 to treat or prevent graft-versus-host disease (GVHD) in a subject.
  • the agent is a monoclonal antibody (e.g., vedolizumab).
  • the GVHD is steroid refractory intestinal GVHD.
  • the subject received corticosteroid therapy prior to or concurrent with the agent.
  • the subject received immunosuppressive therapy prior to or concurrent with the agent.
  • the subject exhibits or does not exhibit symptoms of GVHD (e.g., steroid refractory intestinal GVHD).
  • graft-versus-host disease comprising: administering an agent that inhibits one or more biological activities of integrin ⁇ 4 ⁇ 7 to the subject.
  • FIG. 1 Colonic biopsies in patients 1 - 3 before (a, c and e) and after (b, d and f) treatment with vedolizumab.
  • Patient 1 had substantial crypt loss and some remaining and regenerating crypts with a few apoptotic bodies, corresponding to GVHD grade III (a).
  • Biopsies taken after vedolizumab showed prominent regenerative changes with crypt branching and crowding, and very few apoptotic bodies. Some areas still lacked crypts and were edematous with capillary dilatation and proliferation and iron-laden macrophages (b). In patient 2, pre-treatment biopsies showed erosions and substantial crypt loss and inflammation, and marked apoptosis in the remaining crypts, corresponding to GVHD grade III(c). After vedolizumab histology showed crypt regeneration and branching with reactive epithelial changes, and no apoptosis or inflammation (d).
  • pre-treatment biopsies showed large eroded areas with crypt loss, numerous apoptotic cells in remaining crypts, and edematous lamin apropria with capillary proliferation and scattered neutrophils, eosinophils, and mononuclear cells.
  • the findings corresponded to GVHD grade III-IV (e).
  • CMV cytomegalovirus
  • FIG. 2 Endoscopic findings in patients 1, 2 and 3.
  • Duodenal mucosa pre-treatment (a,b and c) and after three doses of vedolizumab (d, e and f).
  • Colonic mucosa in patient 1 pre- treatment (g) and after three doses (j).
  • Ileal mucosa in patient 2 pre- and post-treatment (h, k) and colonic mucosa in patient 3 pre- and post-treatment (i, 1)
  • the term “subject” refers to any animal (e.g., a mammal), including, but not limited to, humans, non-human primates, rodents, and the like, which is to be the recipient of a particular treatment.
  • the terms “subject” and “patient” are used interchangeably herein in reference to a human subject.
  • non-human animals refers to all non-human animals including, but not limited to, vertebrates such as rodents, non-human primates, ovines, bovines, ruminants, lagomorphs, porcines, caprines, equines, canines, felines, aves, etc.
  • sample is used in its broadest sense. In one sense, it is meant to include a specimen or culture obtained from any source, as well as biological and environmental samples. Biological samples may be obtained from animals (including humans) and encompass fluids, solids, tissues, and gases. Biological samples include blood products, such as plasma, serum and the like. Environmental samples include environmental material such as surface matter, soil, water, crystals and industrial samples. Such examples are not however to be construed as limiting the sample types applicable to the present invention.
  • drug is meant to include any molecule, molecular complex or substance administered to an organism for diagnostic or therapeutic purposes, including medical imaging, monitoring, contraceptive, cosmetic, nutraceutical, pharmaceutical and prophylactic applications.
  • drug is further meant to include any such molecule, molecular complex or substance that is chemically modified and/or operatively attached to a biologic or biocompatible structure.
  • the term “purified” or “to purify” or “compositional purity” refers to the removal of components (e.g., contaminants) from a sample or the level of components (e.g. , contaminants) within a sample. For example, unreacted moieties, degradation products, excess reactants, or byproducts are removed from a sample following a synthesis reaction or preparative method.
  • test compound and “candidate compound” refer to any chemical entity, pharmaceutical, drug, and the like that is a candidate for use to treat or prevent a disease, illness, sickness, or disorder of bodily function (e.g., cancer).
  • Test compounds comprise both known and potential therapeutic compounds.
  • a test compound can be determined to be therapeutic by screening using screening methods known in the art.
  • the present invention relates to methods for the treatment of graft-versus-host disease (GVHD).
  • GVHD graft-versus-host disease
  • the present invention relates to methods of treating GVHD with agents that target integrin ⁇ 4 ⁇ 7.
  • Vedolizumab a monoclonal antibody targeting the homing of T-cells to the intestinal endothelium through inhibition of binding of integrin ⁇ 4 ⁇ 7 to the mucosal addressin
  • MadCAM-1 has been effective in inflammatory bowel disease (IBD) (3-5). As it is selective for receptors in the gut, it has not been associated with progressive multifocal
  • PML leukencephalopathy
  • Acute GvHD is an immunologically mediated disease where alloreactive donor T- cells are important contributors to the pathogenesis (6). Inhibiting T-cell induced
  • the ⁇ 4 ⁇ 7 integrin is expressed on lymphocytes, natural killer cells, mast cells and basophilic granulocytes and mediate lymphocyte binding to MAdCAM-1 (7).
  • This intestinal specificity makes the interaction an attractive target for treating immunologically mediated disease of the intestine, such as GvHD in allogeneic stem cell transplantation (8) .
  • Expression of ⁇ 4 ⁇ 7 on donor T-cells have been described to be important in the development of intestinal GvHD in mice (9, 10). Choi et al have reported that disruption of alloreactive donor T-cell trafficking to the target organs significantly reduces GvHD in both MHC fully - mismatched and minor-mismatched allo-HCT models (11).
  • the adhesion molecule MAdCAM-1 belongs to the immunoglobulin superfamily. It is constitutively expressed on high endothelial venules of both mesenteric lymph nodes and Peyers patches (PP) as well as on postcapillary venules of the lamina intestinal of the small and large intestine. PPs are essential in the development of anti-host cytotoxic T-cells leading to acute intestinal GvHD (12).
  • MAdCAM-1 is the major ligand for ⁇ 4 ⁇ 7 integrin, as well as being the ligand for L-selectin (13).
  • the expression level of ⁇ 4 ⁇ 7 integrin is relatively low on naive T-cells and B-cells, but increased on IgA-secreting plasma cells, memory T cells, and activated gut- homing CD4+ T-cells.
  • ⁇ 4 ⁇ 7 integrin is expressed on NK-cells, activated monocytes, macrophages, eosinophils, and dendritic cells (14).
  • GVHD e.g., steroid refractory acute GVHD
  • agents that inhibit integrin ⁇ 4 ⁇ 7 e.g., integrin ⁇ 4 ⁇ 7
  • subjects are at risk for GVHD (e.g., steroid refractory acute GVHD).
  • GVHD e.g., steroid refractory acute GVHD
  • subjects have undergone an organ transplant and have no symptoms of GVHD.
  • subjects have initial symptoms of GVHD.
  • subjects have symptoms of GVHD but not steroid refractory acute GVHD.
  • subjects have symptoms of steroid refractory acute GVHD.
  • subjects are monitored for symptoms or markers of GVHD before, during, or after treatment with vedolizumab.
  • a treatment course of action (e.g., starting, stopping, or adjusting the dosage) of vedolizumab) based on the results of the monitoring.
  • the monitoring is repeated one or more times before, during, or after treatment with vedolizumab.
  • subjects have previously or are currently being treated with an immunosuppressant (e.g., steroid therapy, antithymocyte globulin (ATG), extracorporeal photopheresis, mycophenolate mofetil (MMF), daclizumab, sirolimus, infliximab, alemtuzumab, methotrexate, basiliximab, tacrolimus, pulses of cyclophosphamide, pentostatin, mesenchymal stromal cells, or etanercept).
  • an immunosuppressant e.g., steroid therapy, antithymocyte globulin (ATG), extracorporeal photopheresis, mycophenolate mofetil (MMF), daclizumab, sirolimus, infliximab, alemtuzumab, methotrexate, basiliximab, tacrolimus, pulses of cyclophosphamide, pentostatin, me
  • Table 1 Patient characteristics are given in Table 1. All patients were categorized as having grade IV intestinal acute GvHD with few or no other manifestations of acute GvHD. Patients 1 and 2 had been through 2nd and 3rd line therapy with several modalities of treatment without improvement of symptoms. Patient 3 to 6 received vedolizumab as second line therapy after steroid failure (table 1). Previous treatments are described in table 1.
  • Vedolizumab was given as described for IBD with 300 mg intravenously without premedication week 0, 2 and 6, followed by infusions every 8 weeks on clinical indication and guided by serum concentration measurements.
  • vedolizumab After three doses of vedolizumab, 4 patients were off systemic corticosteroids. Five out of six patients received oral medication, including immunosuppressants. Concomitant immunosuppressive therapy was administered as oral cyclosporine or MMF. There were no or limited clinical symptoms of acute intestinal GvHD, maximum, grade I. Five out of six patients could be discharged from hospital after the third dose of vedolizumab. Patient 2 initially achieved a complete response after three doses of vedolizumab, but experienced a relapse of AML and developed grade IV intestinal GvHD after cessation of
  • Patient 3 developed acute GvHD of the skin after discharge from hospital and high dose corticosteroids were reinstitued, subsequently complicated by staphylococcal sepsis and acute respiratory distress syndrome leading to death.
  • Patient 4 already had multi-organ failure with hemodialysis and liver failure prior to start of vedolizumab treatment. She succumbed to complications. An autopsy was declined.
  • Patients 1 and 2 are receiving continuous treatment with vedolizumab 12 months after start of treatment and display no or limited symptoms of intestinal GvHD. Patients 5 and 6 did not require additional treatment after the 2. and 3. dose.
  • Acute GvHD remains the major cause of non-relapse mortality after allogeneic stem cell transplantation. This case series provides proof that targeting integrin ⁇ 4 ⁇ 7 is feasible and may provide clinical meaningful responses in steroid refractory intestinal GvHD. The mechanism is probably a direct inhibition of homing of allo-reactive T-cells to the intestinal endothelium.
  • MAdCAM-1 is not only an organ- and stimulus-specific adhesive determinant, but is also density dependent, suggesting that its highly restricted expression is decisively related to particular phases in inflammation (17).
  • MadCAM-1 is constitutively expressed on high endothelial venules of both mesenteric lymph nodes and PPs. Inhibition of ⁇ 4 ⁇ 7 integrin may not only affect T-cell homing to the intestine, but also homing of other cells that are important for initiating and propagating an allo-response, such as dendritic cells and NK-cells.
  • vedolizumab will primarily be effective in intestinal GvHD, and should probably not be used as a single agent in the treatment of acute GvHD involving other tissues.
  • Lam MC Bressler B. Vedolizumab for ulcerative colitis and Crohn's disease: results and implications of GEMINI studies. Immunotherapy.6(9):963-71.
  • Petrovic A Alpdogan O, Willis LM, et al. LP AM (alpha 4 beta 7 integrin) is an important homing integrin on alloreactive T cells in the development of intestinal graft- versus-host disease. Blood. 2004 Feb 15;103(4): 1542-7.

Landscapes

  • Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Transplantation (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

La présente invention concerne des méthodes pour le traitement d'une maladie du greffon contre l'hôte (GVH). En particulier, la présente invention concerne des méthodes de traitement de GVH avec des agents qui ciblent l'intégrine α4β7.
PCT/IB2016/000440 2016-03-18 2016-03-18 Méthodes de traitement d'une maladie du greffon contre l'hôte Ceased WO2017158393A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/IB2016/000440 WO2017158393A1 (fr) 2016-03-18 2016-03-18 Méthodes de traitement d'une maladie du greffon contre l'hôte

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IB2016/000440 WO2017158393A1 (fr) 2016-03-18 2016-03-18 Méthodes de traitement d'une maladie du greffon contre l'hôte

Publications (1)

Publication Number Publication Date
WO2017158393A1 true WO2017158393A1 (fr) 2017-09-21

Family

ID=55809150

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2016/000440 Ceased WO2017158393A1 (fr) 2016-03-18 2016-03-18 Méthodes de traitement d'une maladie du greffon contre l'hôte

Country Status (1)

Country Link
WO (1) WO2017158393A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12304956B1 (en) 2023-05-30 2025-05-20 Paragon Therapeutics, Inc. Dosing regimen for treating inflammatory bowel disease

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007061679A1 (fr) * 2005-11-17 2007-05-31 Millennium Pharmaceuticals, Inc. IMMUNOGLOBULINE HUMANISEE REACTIVE AVEC L’INTEGRINE α4β7
WO2012151248A2 (fr) * 2011-05-02 2012-11-08 Millennium Pharmaceuticals, Inc. FORMULATION POUR UN ANTICORPS ANTI-α4β7

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007061679A1 (fr) * 2005-11-17 2007-05-31 Millennium Pharmaceuticals, Inc. IMMUNOGLOBULINE HUMANISEE REACTIVE AVEC L’INTEGRINE α4β7
WO2012151248A2 (fr) * 2011-05-02 2012-11-08 Millennium Pharmaceuticals, Inc. FORMULATION POUR UN ANTICORPS ANTI-α4β7

Non-Patent Citations (21)

* Cited by examiner, † Cited by third party
Title
"7 Westferry Circus ● Canary Wharf ● London E14 4HB ● United Kingdom An agency of the European Union EPAR summary for the public", 1 June 2014 (2014-06-01), XP055253848, Retrieved from the Internet <URL:http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/002782/WC500168532.pdf> [retrieved on 20160229] *
"ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS", 16 June 2014 (2014-06-16), XP055253845, Retrieved from the Internet <URL:http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002782/WC500168528.pdf> [retrieved on 20160229] *
ALEXANDER JS; ANDO T.: "Density-dependent control of MAdCAM-1 and chronic inflammation. Focus on ''Mechanisms of MAdCAM-1 gene expression in human intestinal microvascular endothelial cells''.", AM J PHYSIOL CELL PHYSIOL., vol. 288, no. 2, February 2005 (2005-02-01), pages 243 - 4
BERLIN C; BERG EL; BRISKIN MJ ET AL.: "Alpha 4 beta 7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1", CELL, vol. 74, no. 1, 16 July 1993 (1993-07-16), pages 185 - 95
CHEN YB; MCDONOUGH S; CHEN H ET AL.: "Expression of alpha4beta7 integrin on memory CD8(+) T cells at the presentation of acute intestinal GVHD", BONE MARROW TRANSPLANT, vol. 48, no. 4, pages 598 - 603
CHOI J; ZIGA ED; RITCHEY J ET AL.: "IFNgammaR signaling mediates alloreactive T-cell trafficking and GVHD", BLOOD, vol. 120, no. 19, pages 4093 - 103
CLAHSEN T; PABST O; TENBROCK K ET AL.: "Localization of dendritic cells in the gut epithelium requires MAdCAM-1", CLIN IMMUNOL., vol. 156, no. 1, pages 74 - 84
COMES JS.: "Number, size, and distribution of Peyer's patches in the human small intestine: Part I The development of Peyer's patches", GUT, vol. 6, no. 3, June 1965 (1965-06-01), pages 225 - 9
DEEG HJ.: "How I treat refractory acute GVHD.", BLOOD, vol. 109, no. 10, 15 May 2007 (2007-05-15), pages 4119 - 26
DUTT S; ERMANN J; TSENG D ET AL.: "L-selectin and beta7 integrin on donor CD4 T cells are required for the early migration to host mesenteric lymph nodes and acute colitis of graft-versus-host disease", BLOOD., vol. 106, no. 12, 1 December 2005 (2005-12-01), pages 4009 - 15
ERIE DJ; BRISKIN MJ; BUTCHER EC ET AL.: "Expression and function of the MAdCAM-1 receptor, integrin alpha 4 beta 7, on human leukocytes", J IMMUNOL., vol. 153, no. 2, 15 July 1994 (1994-07-15), pages 517 - 28
KANDA J; HISHIZAWA M; UTSUNOMIYA A ET AL.: "Impact of graft-versus-host disease on outcomes after allogeneic hematopoietic cell transplantation for adult T-cell leukemia: a retrospective cohort study", BLOOD., vol. 119, no. 9, pages 2141 - 8
KNUT LUNDIN ET AL: "Vedolizumab in Treatment of Severe Intestinal Graft Versus Host Disease", INFLAMMATORY BOWEL DISEASES, 1 March 2016 (2016-03-01), XP055283741, Retrieved from the Internet <URL:http://pdfs.journals.lww.com/ibdjournal/2016/03001/P_067_Vedolizumab_in_Treatment_of_Severe.92.pdf?token=method|ExpireAbsolute;source|Journals;ttl|1467020044051;payload|mY8D3u1TCCsNvP5E421JYK6N6XICDamxByyYpaNzk7FKjTaa1Yz22MivkHZqjGP4kdS2v0J76WGAnHACH69s21Csk0OpQi3YbjEMdSoz2UhVybFqQxA7lKwSUlA502zQZr9> [retrieved on 20160627] *
KOMGOLD R; SPRENT J.: "Lethal graft-versus-host disease after bone marrow transplantation across minor histocompatibility barriers in mice. Prevention by removing mature T cells from marrow", J EXP MED, vol. 148, no. 6, 1 December 1978 (1978-12-01), pages 1687 - 98
LAM MC; BRESSLER B.: "Vedolizumab for ulcerative colitis and Crohn's disease: results and implications of GEMINI studies", IMMUNOTHERAPY, vol. 6, no. 9, pages 963 - 71
MILCH C; WYANT T; XU J ET AL.: "Vedolizumab, a monoclonal antibody to the gut homing alpha4beta7 integrin, does not affect cerebrospinal fluid T-lymphocyte immunophenotype", J NEUROIMMUNOL., vol. 264, no. 1-2, pages 123 - 6
MURAI M; YONEYAMA H; EZAKI T ET AL.: "Peyer's patch is the essential site in initiating murine acute and lethal graft-versus-host reaction.", NAT IMMUNOL., vol. 4, no. 2, February 2003 (2003-02-01), pages 154 - 60
PETROVIC A; ALPDOGAN O; WILLIS LM ET AL.: "LP AM (alpha 4 beta 7 integrin) is an important homing integrin on alloreactive T cells in the development of intestinal graft-versus-host disease", BLOOD, vol. 103, no. 4, 15 February 2004 (2004-02-15), pages 1542 - 7
SOLER D; CHAPMAN T; YANG LL ET AL.: "The binding specificity and selective antagonism of vedolizumab, an anti-alpha4beta7 integrin therapeutic antibody in development for inflammatory bowel diseases", J PHARMACOL EXP THER., vol. 330, no. 3, September 2009 (2009-09-01), pages 864 - 75
VAN KRUININGEN HJ; WEST AB; FREDA BJ ET AL.: "Distribution of Peyer's patches in the distal ileum", INFLAMM BOWEL DIS, vol. 8, no. 3, May 2002 (2002-05-01), pages 180 - 5
YNGAR FLOISAND ET AL: "Paper: Targeting Integrin a4b7-Expressing T-Cells in Steroid Refractory Intestinal GvHD", CLINICAL ALLOGENEIC TRANSPLANTATION: ACUTE AND CHRONIC GVHD, IMMUNE RECONSTITUTION, 6 December 2015 (2015-12-06), XP055283730, Retrieved from the Internet <URL:https://ash.confex.com/ash/2015/webprogram/Paper79717.html> [retrieved on 20160627] *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12304956B1 (en) 2023-05-30 2025-05-20 Paragon Therapeutics, Inc. Dosing regimen for treating inflammatory bowel disease
US12404334B2 (en) 2023-05-30 2025-09-02 Paragon Therapeutics, Inc. Methods of treating gastrointestinal inflammatory disease

Similar Documents

Publication Publication Date Title
Zundler et al. Gut immune cell trafficking: inter-organ communication and immune-mediated inflammation
Stokes et al. Development of glomerulonephritis during anti-TNF-α therapy for rheumatoid arthritis
Fløisand et al. Targeting integrin α4β7 in steroid-refractory intestinal graft-versus-host disease
Trivedi et al. Chemokines and chemokine receptors as therapeutic targets in inflammatory bowel disease; pitfalls and promise
Li et al. Immunoproteasome inhibition prevents chronic antibody-mediated allograft rejection in renal transplantation
Kerfoot et al. Overlapping roles of P-selectin and α4 integrin to recruit leukocytes to the central nervous system in experimental autoimmune encephalomyelitis
Tsukada et al. Blockade of CD134 (OX40)-CD134L interaction ameliorates lethal acute graft-versus-host disease in a murine model of allogeneic bone marrow transplantation
Xu et al. Modulation of endothelial cell function by normal polyspecific human intravenous immunoglobulins: a possible mechanism of action in vascular diseases
Villablanca et al. Blocking lymphocyte localization to the gastrointestinal mucosa as a therapeutic strategy for inflammatory bowel diseases
Xu et al. Selective targeting of the LIGHT-HVEM costimulatory system for the treatment of graft-versus-host disease
Oberoi et al. Anti-tumor necrosis factor-α therapy increases plaque burden in a mouse model of experimental atherosclerosis
Gwyer Findlay et al. OX40L blockade is therapeutic in arthritis, despite promoting osteoclastogenesis
US9156912B2 (en) Immunological reconstitution promoter or prophylactic agent for infections each of which maintains graft-versus-tumor effect
Nair et al. Current and future challenges in therapy for antibody-mediated rejection
Johnston et al. Administration of anti-CD20 mAb is highly effective in preventing but ineffective in treating chronic graft-versus-host disease while preserving strong graft-versus-leukemia effects
Bakshi et al. New therapeutic avenues in SLE
Jennette et al. Pathogenesis of vasculitis
EP4294841A1 (fr) Méthodes et matériaux pour le traitement d&#39;expansions de cellules t clonales
US20090297502A1 (en) Ccr2 antagonists for chronic organ transplantation rejection
Kuroda et al. A case of AA amyloidosis associated with rheumatoid arthritis effectively treated with Infliximab
ES2348984T3 (es) Procedimientos de tratamiento de la aterosclerosis.
WO2017158393A1 (fr) Méthodes de traitement d&#39;une maladie du greffon contre l&#39;hôte
EP2282760B1 (fr) Procédé de traitement ou de prophylaxie de maladies intestinale inflammatoire
Sands et al. Geoepidemiology and autoimmune manifestations of lymphoproliferative disorders
Huang et al. A novel apoptosis‐inducing anti‐PSGL‐1 antibody for T cell‐mediated diseases

Legal Events

Date Code Title Description
NENP Non-entry into the national phase

Ref country code: DE

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 16718725

Country of ref document: EP

Kind code of ref document: A1

122 Ep: pct application non-entry in european phase

Ref document number: 16718725

Country of ref document: EP

Kind code of ref document: A1