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WO1997036602A1 - Procede pour reconstituer une proteine fonctionnelle dans un tissu par transplantation de cellules - Google Patents

Procede pour reconstituer une proteine fonctionnelle dans un tissu par transplantation de cellules Download PDF

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Publication number
WO1997036602A1
WO1997036602A1 PCT/CA1996/000191 CA9600191W WO9736602A1 WO 1997036602 A1 WO1997036602 A1 WO 1997036602A1 CA 9600191 W CA9600191 W CA 9600191W WO 9736602 A1 WO9736602 A1 WO 9736602A1
Authority
WO
WIPO (PCT)
Prior art keywords
cells
transplantation
muscle
lama2
cell
Prior art date
Application number
PCT/CA1996/000191
Other languages
English (en)
Inventor
Jacques P. Tremblay
Raynald Roy
Jean-Thomas Vilquin
Benoit Guerette
Original Assignee
Universite Laval
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 Universite Laval filed Critical Universite Laval
Priority to PCT/CA1996/000191 priority Critical patent/WO1997036602A1/fr
Priority to EP96907971A priority patent/EP0896542A1/fr
Priority to CA002260808A priority patent/CA2260808A1/fr
Priority to AU51401/96A priority patent/AU5140196A/en
Publication of WO1997036602A1 publication Critical patent/WO1997036602A1/fr

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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
    • C07K16/2803—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 immunoglobulin superfamily
    • 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
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/34—Muscles; Smooth muscle cells; Heart; Cardiac stem cells; Myoblasts; Myocytes; Cardiomyocytes
    • 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
    • C07K16/2845—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 beta2-subunit-containing molecules, e.g. CD11, CD18
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • This invention relates to a method of restoring a
  • donor cells or genetically modified donor cells. More
  • the present method reduces the mortality
  • Myoblast transplantation may indeed be any one of several diseases. Myoblast transplantation may indeed be any one of several diseases. Myoblast transplantation may indeed be any one of several diseases. Myoblast transplantation may indeed be any one of several diseases. Myoblast transplantation may indeed be any one of several diseases. Myoblast transplantation may indeed be any one of several diseases. Myoblast transplantation may indeed be any one of several diseases. Myoblast transplantation may indeed be any one of several diseases. Myoblast transplantation may indeed be transplantation of several diseases.
  • transplantation may be used to treat Huntington disease
  • islet may be use for diabetic (Hering et al. 1993), hepatocytes for liver diseases (Raper and
  • transplantation are the following:
  • infiltrating cells may be observed at the site of
  • histocompatible host and donor are selected (matched for
  • antigens might be responsible for an observed immune
  • fibroblast growth factor is shown to increase by four ⁇
  • Inflammation may be one of the major factors involved in
  • Inflammation may be also a cell or humoral response. Inflammation may be also a cell or humoral response. Inflammation may be also a cell or humoral response. Inflammation may be also a cell or humoral response. Inflammation may be also a cell or humoral response. Inflammation may be also a cell or humoral response. Inflammation may be also a cell or humoral response. Inflammation may be also a cell or humoral response. Inflammation may be also
  • dystrophic mouse which was used was (C57BL/6J-dy 2 /dy 2J )
  • fibroblasts interfere with the practice of the claimed invention and cause detrimental
  • merosin a protein called merosin (Arahata et al . 1993; Sunada et
  • mice have an
  • Dr. Law's group is erroneous and thus the scientific
  • transplant survival one of the most serious problems: transplant survival.
  • tissue which comprises the steps of transplanting donor cells in a patient in need for such a transplantation
  • transplantation being made in the presence of an
  • blocking is effected by using an anti-ICAM-1 antibody
  • MHC class I and class II antigens MHC class I and class II antigens
  • immunosuppressive agents are rapamycin or FK506,
  • the immunosuppressors are used.
  • the donor cells might be selected from the group
  • these cells may be transplanted from a donor biopsy, these cells may be
  • the used promoter might be an inducible promoter.
  • cell proliferation is SV40-T antigen.
  • the promoter is SV40-T antigen.
  • this promoter is a MHC Class II gene
  • a MHC Class II promoter is inducible by ⁇ -
  • thermosensitive mutants thereof may be used.
  • myogenic cells may be required while for
  • the present invention provides for the first
  • transplantation of myoblasts eg. restoration of
  • dystrophin or the transplantation of non myogenic cells (eg. restoration of merosin) will achieve such results
  • the invention is based on successful
  • myoblasts by forming new muscle fibers or forming hybrid
  • muscle cells i.e. by fusing with host myoblasts or muscle fibers
  • the missing gene product e.g.
  • the missing gene product eg.
  • merosin may be secreted in the extracellular matrix.
  • the myogenic or non myogenic cells to be used.
  • transplanted can be histocompatible or histoincompatible
  • pharmacological agents such as cyclosporin-A, rapamycin
  • the immunosuppression may also be
  • lymphocytes or antigen presenting cell determinants are lymphocytes or antigen presenting cell determinants.
  • CD4 , anti-CD8 and anti-LFA-1 Mabs were both capable of
  • immunosuppressive agents may maintain long-term graft
  • the immunosuppressive treatment may therefore be any immunosuppressive treatment.
  • the used of mAbs may eventually lead to permanent
  • the myogenic and the non myogenic cells may be any type of myogenic and the non myogenic cells.
  • founders may also be facilitated by introducing in the founder
  • cloned cells may also prevent undesired
  • a mouse cell line MB3 has been produced which
  • transplanted cells by introducing a ⁇ -IFN inducible SV40 T antigen may be subject to variation, as will be
  • reaction may be effected on a biopsy.
  • cDNAs so amplified may have a differential restriction
  • transplanted myoblasts may be monitored by way of
  • the amount of cells to be injected may depend of
  • the muscle may be facilitated by developing a device
  • This robotic device may receive
  • the imaging system e.g. magnetic scanner
  • the cells required to treat the muscle may also be treated.
  • Some type of cells may be inserted by some other routes.
  • the solution to inject the cells may range from
  • the injection solution may also contains
  • invention is to enhance the early survival rate of
  • mice are an animal model of Duchenne
  • this animal model lacks dystrophin due to a
  • myoblasts may be grown from a muscle biopsy of an
  • the host may be im uno-
  • Myogenic cells have been shown to be able to form
  • the injected myoblasts can be
  • new muscle fibers can be formed in a primate.
  • retrovirus vector containing the ⁇ -galactosidase gene
  • Duchenne muscular dystrophy is due to the absence
  • the protein can be any of dystrophin in the muscle fibers.
  • the protein can be any of dystrophin in the muscle fibers.
  • the protein can be any of dystrophin in the muscle fibers.
  • the protein can be any of dystrophin in the muscle fibers.
  • the protein can be any of dystrophin in the muscle fibers.
  • the protein can be any of dystrophin in the muscle fibers.
  • the protein can be any of dystrophin in the muscle fibers.
  • the muscular dystrophy in dy/dy mice is due to the
  • Muscular Dystrophy (Arahata et al . 1993; Sunada et al .
  • merosin can be restored by the transplantation in the
  • extracellular matrix stabilizes the muscle fibers.
  • mice The C57BL/6J dy/dy mice (Jackson Lab.) were used as the mice.
  • the transgenic TnI-LacZV29 mice (Tn-LacZ, gift from
  • ⁇ -gal cytoplasmic ⁇ -galactosidase
  • ⁇ -gal expression is not restricted to the nucleus in
  • the H-2K b -tsA58 transgenic mice carry the
  • thermolabile tsA58 mutant of SV40 large T antigen under
  • Interferon Y (IFN- ⁇ ) increases the transcription of this
  • thermolabile protein is functionally
  • H-2K -tsA58 male mouse (Charles River Lab., Wilmington,
  • the cell suspension was cultured in 199 medium (Gibco, Grand Island, NY)
  • FCS concentration to 5% and growing the cells at 37°C in
  • Tibialis anterior (TA) muscles were exposed and injected
  • transplantation three days before transplantation, one
  • histochemistry was as sensitive as three-step
  • the second antibody was FITC-conjugated rabbit anti-mouse IgG (1/100 in PBS
  • hybrid muscle fibers expressing ⁇ -gal hybrid muscle fibers expressing ⁇ -gal. These ⁇ -gal
  • LAMA2-positive fibers was low (mean ⁇ SD, 6.4 ⁇ 4.4)
  • the Tn-LacZ primary muscle cultures originate from
  • mice with normal LAMA2 expression mice with normal LAMA2 expression.
  • LAMA2 and ⁇ -gal were present in the donor cells.
  • LAMA2 and ⁇ -gal were present in the donor cells.
  • LAMA2-positive fibers were
  • LAMA2 deposition also presented important
  • mice without inducing tumors.
  • the transgenic myoblasts are mice, without inducing tumors.
  • mice were able to grow and proliferate at 33°C in a 10% C0 2 atmosphere when stimulated by murine IFN- ⁇ .
  • filament desmin which is an early marker of myoblasts
  • myoblasts were thus able to fuse together or with host
  • LAMA2-surrounded fibers were obtained when young animals
  • mice mice were treated with mdx/mdx (Wakeford et al . , 1991) mice. This treatment
  • mRNA are detected in untreated dy/dy mice by RT-PCR
  • LAMA2 LAMA2
  • transplantation is less efficient in dy/dy mouse than in
  • the dy/dy muscle fibers are smaller than
  • the myoblast proliferation and/or migration could be any type of myoblast proliferation and/or migration.
  • LAMA2 was generally more
  • ⁇ -gal expression is restricted to skeletal muscle cells
  • myoblasts or fibroblast-like, or both cell types in the
  • ⁇ -gal positive or LAMA2-positive, or both ⁇ -gal and
  • LAMA2-positive fibers should be observed. LAMA2 expression pa t tern
  • LAMA2 may diffuse, thus producing a gradient of LAMA2
  • LAMA2 is also less in small-diameter than
  • LAMA2 may be secreted by
  • myogenic cells as are other muscle proteins and
  • muscle regeneration that is, myoblast proliferation, alignment or fusion, or the stability of nerve-muscle
  • LAMA2-secreting cell is a connective cell, with no
  • herpesviruses should indicate if it could constitute a
  • Myoblast transplantation may indeed be
  • transplantation may be used to treat Huntington disease
  • islet may be use for diabetic (Hering
  • myoblasts were transplanted in a host previously
  • mice ⁇ -Gal labelled myoblasts were injected in mice
  • cells/section i.e. macrophages and
  • neutrophils The presence of neutrophils was also
  • the death of the transplanted cell is due to an
  • transplanted cells was, however, significantly reduced to only 18.2 ⁇ 7.2% by injecting the host with a mAb

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Developmental Biology & Embryology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Cell Biology (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Virology (AREA)
  • Zoology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

L'invention concerne une méthode pour améliorer les chances de réussite d'une transplantation. Cette invention vise à résoudre, en particulier, un des problèmes les plus sérieux rencontrés lors de transplantations, qui est celui de la survie du transplant. La méthode consiste à transplanter les cellules du donneur sur un patient nécessitant une telle transplantation, la transplantation étant faite en présence d'un agent bloquant l'interaction entre une molécule ICAM-1, se trouvant sur la surface de la membrane des cellules du donneur et la molécule LFA-1, située sur la surface des membranes des leucocytes du patient, ce blocage améliorant la viabilité desdites cellules transplantées du donneur par un facteur d'au moins quatre. L'agent bloquant cette interaction est un anticorps anti-LFA-1 qui est injecté à l'hôte au moment de la transplantation ou un fragment d'anticorps anti-ICAM-1 qui n'est pas capable de fixer le complément, par exemple le fragment F(ab)2.
PCT/CA1996/000191 1996-03-29 1996-03-29 Procede pour reconstituer une proteine fonctionnelle dans un tissu par transplantation de cellules WO1997036602A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
PCT/CA1996/000191 WO1997036602A1 (fr) 1996-03-29 1996-03-29 Procede pour reconstituer une proteine fonctionnelle dans un tissu par transplantation de cellules
EP96907971A EP0896542A1 (fr) 1996-03-29 1996-03-29 Procede pour reconstituer une proteine fonctionnelle dans un tissu par transplantation de cellules
CA002260808A CA2260808A1 (fr) 1996-03-29 1996-03-29 Procede pour reconstituer une proteine fonctionnelle dans un tissu par transplantation de cellules
AU51401/96A AU5140196A (en) 1996-03-29 1996-03-29 Method of restoring a functional protein in a tissue by cell transplantation

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CA1996/000191 WO1997036602A1 (fr) 1996-03-29 1996-03-29 Procede pour reconstituer une proteine fonctionnelle dans un tissu par transplantation de cellules

Publications (1)

Publication Number Publication Date
WO1997036602A1 true WO1997036602A1 (fr) 1997-10-09

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Application Number Title Priority Date Filing Date
PCT/CA1996/000191 WO1997036602A1 (fr) 1996-03-29 1996-03-29 Procede pour reconstituer une proteine fonctionnelle dans un tissu par transplantation de cellules

Country Status (3)

Country Link
EP (1) EP0896542A1 (fr)
AU (1) AU5140196A (fr)
WO (1) WO1997036602A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999030730A1 (fr) * 1997-12-15 1999-06-24 Universite Laval Procedes et compositions permettant d'ameliorer la reussite de la transplantation cellulaire chez un receveur

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993024151A1 (fr) * 1992-05-29 1993-12-09 The General Hospital Corporation Injection de myoblastes par voie arterielle
WO1994004188A1 (fr) * 1992-08-21 1994-03-03 Genentech, Inc. Procede pour traiter une affection ayant pour origine l'antigene 1 associe a la fonction lymphocytaire
WO1995014079A1 (fr) * 1993-11-16 1995-05-26 Indiana University Foundation Greffes myocardiques et compositions cellulaires utiles pour lesdites greffes

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993024151A1 (fr) * 1992-05-29 1993-12-09 The General Hospital Corporation Injection de myoblastes par voie arterielle
WO1994004188A1 (fr) * 1992-08-21 1994-03-03 Genentech, Inc. Procede pour traiter une affection ayant pour origine l'antigene 1 associe a la fonction lymphocytaire
WO1995014079A1 (fr) * 1993-11-16 1995-05-26 Indiana University Foundation Greffes myocardiques et compositions cellulaires utiles pour lesdites greffes

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
A. CHAHINE ET AL.: "Immunomodulation of pancreatic islet allografts in mice with CTLA4Ig secreting muscle cells.", TRANSPLANTATION, vol. 59, no. 9, 1995, BALTIMORE, MD, USA, pages 1313 - 1318, XP000611823 *
A. TALENTO ET AL.: "A single administration of LFA-1 antibody confers prolonged allograft survival.", TRANSPLANTATION, vol. 55, no. 2, February 1993 (1993-02-01), BALTIMORE, MD, USA, pages 418 - 422, XP002019790 *
B. GUÉRETTE ET AL.: "Prevention of immune reactions triggered by first-generation adenoviral vectors by monoclonal antibodies and CTLA4Ig.", HUMAN GENE THERAPY, vol. 7, no. 12, 1 August 1996 (1996-08-01), NEW YORK, NY, USA, pages 1455 - 1463, XP000611510 *
H. YANG ET AL.: "Prolongation of rat islet allograft survival by treatment with monoclonal antibodies against VLA-4 and LFA-1.", TRANSPLANTATION, vol. 60, no. 1, 15 July 1995 (1995-07-15), BALTIMORE, MD, USA, pages 71 - 76, XP000611504 *
I. KINOSHITA ET AL.: "Myoblast allotransplantation in primates.", MUSCLE AND NERVE, vol. 18, no. 10, October 1995 (1995-10-01), BOSTON, MA, USA, pages 1217 - 1218, XP000611723 *
J-T. VILQUIN ET AL.: "FK506 immunosuppression to control the immune reactions triggered by first generation adenovirus-mediated gene transfer.", HUMAN GENE THERAPY, vol. 6, no. 11, November 1995 (1995-11-01), NEW YORK, NY, USA, pages 1391 - 1401, XP000611509 *
M. ISOBE ET AL.: "Specific acceptance of cardiac allograft after treatment with antibodies to ICAM-1 and LFA-1.", SCIENCE, vol. 255, no. 5048, 28 February 1992 (1992-02-28), WASHINGTON, DC, USA, pages 1125 - 1127, XP002019791 *
Y. ZENG ET AL.: "Inhibition of transplant rejection by pretreatment of xenogeneic pancreatic islet cells with anti-ICAM-1 antibodies.", TRANSPLANTATION, vol. 58, no. 6, 27 September 1994 (1994-09-27), BALTIMORE, MD, USA, pages 681 - 689, XP000611506 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999030730A1 (fr) * 1997-12-15 1999-06-24 Universite Laval Procedes et compositions permettant d'ameliorer la reussite de la transplantation cellulaire chez un receveur

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Publication number Publication date
EP0896542A1 (fr) 1999-02-17
AU5140196A (en) 1997-10-22

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