+

WO1993007900A1 - Perfusion in vitro de greffes de reins avec des anticorps - Google Patents

Perfusion in vitro de greffes de reins avec des anticorps Download PDF

Info

Publication number
WO1993007900A1
WO1993007900A1 PCT/GB1992/001890 GB9201890W WO9307900A1 WO 1993007900 A1 WO1993007900 A1 WO 1993007900A1 GB 9201890 W GB9201890 W GB 9201890W WO 9307900 A1 WO9307900 A1 WO 9307900A1
Authority
WO
WIPO (PCT)
Prior art keywords
antibody
kidney
mab
perfused
volume
Prior art date
Application number
PCT/GB1992/001890
Other languages
English (en)
Inventor
Hirsch David Taube
Lawrence Charles Goldberg
Original Assignee
Cantab Pharmaceuticals Research Limited
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
Priority claimed from GB919122160A external-priority patent/GB9122160D0/en
Application filed by Cantab Pharmaceuticals Research Limited filed Critical Cantab Pharmaceuticals Research Limited
Priority to EP92921156A priority Critical patent/EP0610257A1/fr
Priority to JP5507533A priority patent/JPH07500331A/ja
Priority to BR9206649A priority patent/BR9206649A/pt
Publication of WO1993007900A1 publication Critical patent/WO1993007900A1/fr

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
    • C07K16/289—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD45
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/10—Preservation of living parts
    • A01N1/12—Chemical aspects of preservation
    • A01N1/122—Preservation or perfusion media
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/10—Preservation of living parts
    • A01N1/12—Chemical aspects of preservation
    • A01N1/122—Preservation or perfusion media
    • A01N1/126—Physiologically active agents, e.g. antioxidants or nutrients
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00—Preservation of bodies of humans or animals, or parts thereof
    • A01N1/10—Preservation of living parts
    • A01N1/16—Physical preservation processes
    • 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
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • This invention relates to the treatment of kidney grafts to reduce the risk of rejection. More particularly it relates to the perfusion of kidneys in vitro with a liquid containing antibodies directed against passenger leukocytes in the kidney.
  • the technique reported involved the preparation of vials containing 2 mg of each antibody in 2 ml phosphate buffered saline.
  • the allograft was prepared for transplantation by standard method.
  • the renal veins were clamped and the contents of the vial in 50 ml Marshall's solution at 4°C were injected into the renal arteries.
  • Biopsy specimens were taken from the majority of transplants prior to wound closure and used to measure allograft uptake of anti-CD45 mAbs. The authors reported that the perfusion technique needs to be improved, as at least 25% of the grafts were poorly perfused with an antibody uptake of less than 50%.
  • the renal vein should be clamped (occluded) during perfusion, so that a hydrostatic pressure is built up, presumably causing the perfusate and antibody to move into the interstitium of the kidney.
  • the volume of liquid is suitably about 50 ml.
  • a small improvement may be obtained by using higher volumes, eg 100 ml, but the risk of rupture of some part of the organ places a practical limit on the volume in the interests of safety, suggesting that volumes significantly higher than 100 ml are best avoided.
  • the concentration of monoclonal antibody would seem to be suitably about 40 ⁇ g/ml. This value would apply to each antibody species if there is more than one to be used. Thus, for example, if the objective is to target a lytic antibody to the passenger leukocytes, then a single lytic mAb could be applied at 40 ⁇ g/ml, or a lytic pair (such as YTH24.5 YTH54.12) applied at 40 ⁇ g/ml each.
  • This low (CI) temperature is not a specific value, but rather is generally that which is achieved by keeping the organ on (melting) ice. It will therefore normally be expected to be in the range 0-4°C, but may rise somewhat, say to 8°C. This latter could particularly be the case when the organ is perfused, since the perfusion liquid will normally have been kept in a refrigerator, where the temperature is not strictly regulated, but may be as high as 8-10°C, even though ideally it should be rather lower, eg around 4-6°C.
  • the organ will warm up from its CI condition to a WI condition.
  • its temperature will be that of the recipient's body when the blood flow is established, but during the operation the organ will warm up prior to opening the blood vessels, possibly reaching a temperature as high as 20°C or so, which would still be regarded as WI, since biological functions, and consequent deterioration of the organ in vitro, are generally active at such temperatures.
  • the present disclosure contemplates incubation of the organ with the mAb in vitro under CI conditions (say, less than 12°C, and preferably less than 8°C) for a period prior to allowing WI conditions to occur during the surgical procedure.
  • This CI incubation time with the mAb is preferably at least 20 minutes, and may be longer, as the data show. This produces a very significant improvement in the % antibody uptake over that reported in Brewer 1989 (supra) and also good antibody saturation levels.
  • the clinical data presented herewith also demonstrate an apparent correlation of this improvement with reduced incidence of graft rejection.
  • Kidneys were obtained from outbred pigs at an abattoir, typically after 20-30 minutes of warm ischaemia. The kidneys were perfused on site via the renal artery, with cold organ preservation solution (OPS * , Royal Free Hospital, London). Kidneys were cold-perfused until the venous effluent, appeared colourless (400-500ml). They were then sealed in polythene bags containing cold OPS, stored on ice, and returned to the laboratory. After the appropriate cold ischaemia time (CIT, see later), redundant non-renal tissue was dissected off, and the kidneys were weighed. The renal veins were next isolated and clamped. * The composition of this is given in Appendix 1 of this description.
  • the mAb employed was a mouse IgG2a anti-pig CD45 (common epitope), Pgl/45.9 (cell line provided by Dr Richard Binns, AFRC, Babraham, Cambridge, England and antibody purified by Cantab Pharmaceuticals Research Limited).
  • the mAb was diluted in various volumes of cold OPS, in 50ml plastic syringes (Sherwood Medical, Ballymoney, Northern Ireland).
  • a 2.6mm diameter Medicut cannula was cut short, and placed on the end of the syringe. This was introduced into the renal artery, which was then sealed by finger pressure alone.
  • the mAb solution was slowly injected at a constant rate of 20ml/minute. The syringe was then removed, and the renal artery left patent (only minimal mAb reflux was observed).
  • the kidneys were returned to the polythene bags employed previously, and again stored on ice. After varying periods of incubation, wedge biopsies were taken, layed on 1.5cm 2 cork tiles coated with Cryo-M-Bed embedding compound (Bright Instrument Co. Ltd., Huntingdon, England), covered with further Cryo-M-Bed, and snap-frozen in liquid nitrogen. Biopsies were stored at -70°C.
  • Study Design Determination of optimal concentration and incubation times of perfused antibody.
  • Three groups of five kidneys were perfused with 4, 2 or 1 mg mAb diluted in 100ml OPS (effective concentrations of 40, 20 and 10 ⁇ g/ml respectively).
  • a volume of 100ml was chosen as this was found to be the largest volume that would not visibly over-distend the kidney or renal vein.
  • Cortical wedge biopsies were then taken at 20, 40 and 60 minutes, 2, 4, 8 and 14 hours post-mAb perfusion.
  • One kidney was subsequently perfused with 6 mg, and one with 8 mg mAb, in 100 ml OPS.
  • CD45+ cells labelled by perfused antibody would stain red.
  • Pgl/45.9 50 ⁇ g/ml in TBS/BSA was incubated on the sections for one hour at room temperature, which would bind to any CD45 antigens not bound by the perfused antibody.
  • Detection was by the subsequent application of 5nm colloidal gold-conjugated goat anti-mouse (GAM) Igs (Biocell Research Laboratories, Edinburgh, UK) for one hour, diluted 1:25 in 5% dried milk powder in TBS.
  • GAM colloidal gold-conjugated goat anti-mouse
  • a negative control perfusion was performed, where one kidney of a pair was perfused with lmg of the mouse IgG2a monoclonal myeloma protein UPC10 (Sigma M7769), diluted in 100 mis OPS, whilst the contra-lateral kidney was perfused with lmg of PG1/45.9 diluted in the same volume.
  • Non ⁇ specific binding of slide-applied Pgl/45.9 was checked by comparing the labelling produced on unperfused pig kidney sections with that produced by substitution of the primary with TBS/BSA or UPC10.
  • Cross-reactivity of the GAM-gold reagent with the RAM-AP reagent was checked each time a new supply or either of these reagents was obtained, by double- labelling perfused kidney sections as described above, but substituting TBS/BSA for Pgl/45.9.
  • Cell counting Biopsies were examined under high power (x400) using a Leitz Laborlux microscope. Field area was calculated as 0.15mm 2 using a stage micrometer (Graticules Ltd.). The field was divided into four quadrants with a cross-lines graticule (Graticules Ltd. ) to aid cell counting. Any cell stained red or black within the interstitium was considered a CD45+ cell.
  • Results are expressed as the median (and range) of the five kidneys within each group. Comparisons of percentage uptake and saturation scores between biopsies and kidneys were made by Wilcoxon rank sum analysis.
  • the median cold ischaemia time prior to mAb perfusion for these 15 kidneys was 3 hours (range 3 - 4 hours).
  • the variation in mAb uptake and antigen saturation with time is shown in Tables la and lb.
  • mAb uptake can be seen to have been rapid, and was maximal within one hour of mAb perfusion.
  • mAb % uptake was similarly good in kidneys perfused with any of the three volumes, whilst CD45 antigen saturation by perfused mAb was consistently better with 40 ⁇ g/ml than with 20 or lO ⁇ g/ml, reaching statistical significance at several time points. No improvement in uptake was seen in two kidneys perfused with 60 or 80 ⁇ g/ml mAb (% uptake 100% and 100%, saturation score 3.0 and 4.0 respectively).
  • Double-staining of the ureteric biopsies revealed that CD45+ cells in the urothelium were well labelled by perfused antibody (median % uptake 100% in all three groups), but that CD45+ cells within the lamina intestinal were variably labelled, with no clear relation to perfusate volume.
  • kidney grafts The effectiveness of anti-dendritic cell treatment of kidney grafts will depend on the specific elimination or inactivation of most or all of these cells, without causing graft damage.
  • the perfusion of monoclonal antibodies into kidneys prior to transplantation offers a means of targeting such cells.
  • Antibody uptake was essentially homogeneous in both the cortex and medulla, using the larger perfusate volumes, and this effect was not diminished by longer cold ischaemia times.
  • HK1 The first, "HK1", was obtained as a nephrectomy from a patient with severe renal artery stenosis. Consequently the organ was diseased, shrunken and scarred.
  • the cold ischaemia time for this kidney was 7 hours (i.e. prior to antibody perfusion).
  • the kidney was perfused (by injection into renal artery) with 4 mg of the rat anti-human IgG2b mAb pair YTH 24.5 and YTH 54.12 [2mg of each antibody] .
  • the total 4 mg mAb was given in a total volume of only 50 ml preservation fluid (RFS) owing to the very small size of this particular kidney.
  • RFS ml preservation fluid
  • each individual antibody was injected into the kidney at a concentration of 40 ⁇ g/ml to provide a total dose of 2 mg of each antibody.
  • the 50 ml volume containing the 2 mg of each antibody was injected over 2.5 minutes.
  • the kidney was left to incubate for 12 hours, and then washed out with 300 mis of ice-cold (approximately 4°C) organ preservation fluid.
  • the washing with preservation fluid was carried out by use of a 1 m gravity controlled drip and took approximately 5 minutes.
  • Measurement of the amount of mAbs which leaked out of the kidney during perfusion, 12 hour incubation, and which were washed out of the kidney were made by collecting of the fluid, and analysis of mAb concentration by a rat IgG2b EIA.
  • HK2 and 3 A pair of human kidneys ( "HK2 and 3") from a single organ donor became available after they were rejected for transplantation purposes in view of mild renal artery stenosis, though the kidneys were normal macroscopically.
  • HK2 was perfused with 4mg of anti-human CD45 mAb pair YTH 24.5 and YTH 54.12 (2 mg of each antibody).
  • the total 4 mg mAb was given in a total volume of 100 mis.
  • each individual antibody was injected into the kidney at a concentration of 20 ⁇ g/ml to provide a total dose of 2 mg of each antibody.
  • the 100 ml volume at 20 ⁇ g/ml was divided between two 50 mis syringes.
  • the slides were then given three further two-minute TBS washes followed by 10 minute reincubations with rabbit anti-rat and rat APAAP reagents respectively, with three two minute TBS washes between and after them.
  • Alkaline phosphatase substrate was then filtered onto the slides and left for 20 minutes.
  • the substrate was composed of naphthol AS-MX di- sodium phosphate salt (Sigma) and Fast Red salt TR (Sigma), with levamisole added to block endogenous alkaline phosphatase activity.
  • Table 3 shows the uptake and saturation of antibody onto human kidneys using the perfusion protocol developed in the pig.
  • the double staining protocol used is shown in Appendix 2.
  • Fig. 3 is a graph showing the relative binding of the two antibodies to a CD45-positive human B cell line called Raji. Relative binding is measured as the mean fluorescence intensity (MFI) in a FACS apparatus.
  • MFI mean fluorescence intensity
  • the graph in Fig. 4 shows the percentage of maximal activity of the antibody pair binding to Raji cells compared to the percentage maximal activity of lysis of Raji cells coated with anti CD45 antibodies in the presence of human complement.
  • the antibody concentration in ⁇ g/ml is the total immunoglobulin concentration while the antibodies are reacting with the cells.
  • the concentration of each antibody separately is one half of the amount shown.
  • the lysis measured by 51 Cr release was carried out essentially as described in Bindon et al 3 replacing Raji cells for human lymphocytes.
  • the antibody binding experiment was carried out as follows. 250,000 Raji cells in 25 microlitres of phosphate buffered saline containing 1% BSA (FACS buffer) were incubated with 25 microlitres of the different concentration of immunoglobulin. After one hour at 4°C the cells were washed three times and the antibody bound to the surface of the cells detected by using a saturating amount of an FITC conjugated affinity purified anti-rat immunoglobulin. The cells were incubated for a further 30 minutes at 4°C washed twice in FACS buffer and once in PBS 1% BSA. The cells were finally resuspended and analyzed on a Becton Dickinson FACS scan using standard procedures.
  • Rat APAAP (Dako D488) 1/25 in TBS/1%BSA, 30 mins RT
  • Biotinylated rat anti-human CD45 (YTH 24.5/54.12 1:1, Cantab Pharmaceuticals Research Ltd), 5 ⁇ g each Mab/ml in TBS/1%BSA 1 hour RT

Landscapes

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

Abstract

Traitement in vitro d'un rein avant sa transplantation chez un receveur humain, de façon à réduire les risques de rejet, comprenant la perfusion du rein avec une solution d'anticorps spécifiques à des leucocytes passagers (par exemple, un anticorps anti-CD45) dans des conditions d'ischémie froide (CI) et d'occlusion de la veine rénale, ainsi que l'incubation du rein perfusé dans des conditions d'ischémie froide pendant au moins 20 minutes. Le volume du liquide de perfusion est, de préférence, au moins de 50 ml et la concentration d'anticorps monoclonaux mAb d'environ 40 νg/ml ou davantage. On a découvert que ce procédé amplifie l'acceptation des anticorps monoclonaux mAb par les cellules cibles, ainsi que le niveau de saturation en anticorps monoclonaux desdites cellules cibles; ledit procédé semble également être associé à une diminution du rejet de la greffe.
PCT/GB1992/001890 1991-10-18 1992-10-15 Perfusion in vitro de greffes de reins avec des anticorps WO1993007900A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP92921156A EP0610257A1 (fr) 1991-10-18 1992-10-15 Perfusion in vitro de greffes de reins avec des anticorps
JP5507533A JPH07500331A (ja) 1991-10-18 1992-10-15 腎臓の移植片の生体外抗体灌流
BR9206649A BR9206649A (pt) 1991-10-18 1992-10-15 Processo para o tratamento in vitro de um rim antes do transplante em um receptor humano

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB919122160A GB9122160D0 (en) 1991-10-18 1991-10-18 Delivery of biological substances
GB9122160.6 1991-10-18
GB929217344A GB9217344D0 (en) 1991-10-18 1992-08-14 Delivery of biological substances
GB9217344.2 1992-08-14

Publications (1)

Publication Number Publication Date
WO1993007900A1 true WO1993007900A1 (fr) 1993-04-29

Family

ID=26299712

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1992/001890 WO1993007900A1 (fr) 1991-10-18 1992-10-15 Perfusion in vitro de greffes de reins avec des anticorps

Country Status (6)

Country Link
EP (1) EP0610257A1 (fr)
JP (1) JPH07500331A (fr)
AU (1) AU2695492A (fr)
BR (1) BR9206649A (fr)
CA (1) CA2121235A1 (fr)
WO (1) WO1993007900A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995013093A1 (fr) * 1993-11-10 1995-05-18 Leiden University Traitement d'un patient avant une transplantation
FR2763072A1 (fr) * 1997-05-12 1998-11-13 Pasteur Merieux Serums Vacc Utilisation d'un anticorps monoclonal anti-lfa1 en transplantation renale
WO1999026974A1 (fr) * 1997-05-27 1999-06-03 Arch Development Corporation Proteines et peptides stimulant la croissance in vitro et in vivo pour cellules epitheliales renales
US5922598A (en) * 1995-03-24 1999-07-13 Organ, Inc. Reducing tissue immunogenicity by induction of apoptosis
RU2169009C2 (ru) * 1994-04-25 2001-06-20 Трастиз Оф Дартмут Колледж Способы индуцирования т-клеточной толерантности к тканевому или органному трансплантату

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20210132644A (ko) * 2018-12-18 2021-11-04 캐터펄트 테라퓨틱스 비.브이. 이식편 대 숙주 질환(GvHD)의 예방 또는 치료를 위한 항-CCR7 mAb의 용도

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991005568A1 (fr) * 1989-10-20 1991-05-02 Lynxvale Ltd. Materiaux et procedes de traitement de tissu etranger

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991005568A1 (fr) * 1989-10-20 1991-05-02 Lynxvale Ltd. Materiaux et procedes de traitement de tissu etranger

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
ANN.SURG., Volume 212, No. 3, September 1990, Christian P. Larsen et al, "The Role of Graft-derived Dendritic Leukocytes in the Rejection of Vascularized Organ Allografts" *
IMMUNOLOGICAL INVESTIGATIONS, Volume 20, No. 3, 1991, M. Krzymanski et al, "Long-standing rat kidney graft survival by a combination of organ perfusion with MHC class II monoclonal antibody and immunosuppression with reduced doses of 15-deoxyspergualin" *
IMMUNOLOGY LETTERS, Volume 29, 1991, Stephen P. Cobbold, "Monoclonal antibody therapy for the induction of transplantation tolerance" *
TRANSPLANTATION PROCEEDINGS, Volume 22, No. 6, December 1990, M.J. Stangl et al, "Graft Pretreatment with Monoclonal Antibodies Prior to Small-Bowel Transplantation" *
TRANSPLANTATION PROCEEDINGS, Volume X, No. 1, February 1987, D. Taube et al, "Pretreatment of Human Renal Allografts With Monoclonal Antibodies to Induce Long-Term Tolerance" *
Y. Brewer et al,"Effect of graft Perfusion with two CD45 monoclonal antibodies on incidence of kidney allograft rejection", 1989, The Lancet *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995013093A1 (fr) * 1993-11-10 1995-05-18 Leiden University Traitement d'un patient avant une transplantation
RU2169009C2 (ru) * 1994-04-25 2001-06-20 Трастиз Оф Дартмут Колледж Способы индуцирования т-клеточной толерантности к тканевому или органному трансплантату
US5922598A (en) * 1995-03-24 1999-07-13 Organ, Inc. Reducing tissue immunogenicity by induction of apoptosis
FR2763072A1 (fr) * 1997-05-12 1998-11-13 Pasteur Merieux Serums Vacc Utilisation d'un anticorps monoclonal anti-lfa1 en transplantation renale
WO1998051343A1 (fr) * 1997-05-12 1998-11-19 Imtix-Sangstat Utilisation d'un anticorps monoclonal anti-lfa1 en transplantation renale
WO1999026974A1 (fr) * 1997-05-27 1999-06-03 Arch Development Corporation Proteines et peptides stimulant la croissance in vitro et in vivo pour cellules epitheliales renales

Also Published As

Publication number Publication date
AU2695492A (en) 1993-05-21
JPH07500331A (ja) 1995-01-12
EP0610257A1 (fr) 1994-08-17
BR9206649A (pt) 1995-10-24
CA2121235A1 (fr) 1993-04-29

Similar Documents

Publication Publication Date Title
Oury et al. Immunocytochemical localization of extracellular superoxide dismutase in human lung
Weyrich et al. Time course of coronary vascular endothelial adhesion molecule expression during reperfusion of the ischemic feline myocardium
Rand et al. Localization of factor-VIII-related antigen in human vascular subendothelium
Singbartl et al. Protection from ischemia-reperfusion induced severe acute renal failure by blocking E-selectin
Ballard et al. Vascular tenascin‐C regulates cardiac endothelial phenotype and neovascularization
Lemoli et al. Concomitant mobilization of plasma cells and hematopoietic progenitors into peripheral blood of multiple myeloma patients: positive selection and transplantation of enriched CD34+ cells to remove circulating tumor cells
Rubenstein et al. Localization of endotoxin in the walls of the peripheral vascular system during lethal endotoxemia.
Wang et al. Optimal changes in portal hemodynamics induced by splenectomy during living donor liver transplantation
Matsuo et al. Role of CD59 in experimental glomerulonephritis in rats
Beiras-Fernandez et al. Influence of polyclonal anti-thymocyte globulins upon ischemia–reperfusion injury in a non-human primate model
US7695712B2 (en) Recovery of tissue function following administration of B cells to injured tissue
Blantz et al. The acute effects of antiglomerular basement membrane antibody upon glomerular filtration in the rat. The influence of dose and complement depletion.
JP2006527229A (ja) 単離された管腔器官及び生体脈管における内皮組織の保存のための方法及び装置
Benck et al. Donor dopamine does not affect liver graft survival: evidence of safety from a randomized controlled trial
WO1993007900A1 (fr) Perfusion in vitro de greffes de reins avec des anticorps
TUso et al. Removal of natural human xenoantibodies to pig vascular endothelium by perfusion of blood through pig kidneys and livers
JPH05501256A (ja) 外来組織を処理するための材料および方法
Liauw et al. Sequential ischemia/reperfusion results in contralateral skeletal muscle salvage
Lau et al. The role of antibodies and von Willebrand factor in discordant pulmonary xenotransplantation
Yoshioka et al. Cellular and non-cellular compositions of crescents in human glomerulonephritis
Tribe et al. A renal biopsy study in toxaemia of pregnancy.
Güven et al. Proximal arteriovenous fistulas in hemodialysis patients: advantages and disadvantages
Wagner et al. IgG and complement-mediated tissue damage in the absence of C2: evidence of a functionally active C2-bypass pathway in a guinea pig model
Chabannon et al. High-dose chemotherapy followed by reinfusion of selected CD34+ peripheral blood cells in patients with poor-prognosis breast cancer: a randomized multicentre study
van Pelt-Verkuil et al. The use of a carbodiimide-containing fixative for the immunohistochemical demonstration of coagulation factor VIII in rat vascular tissue

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AT AU BB BG BR CA CH CS DE DK ES FI GB HU JP KP KR LK LU MG MN MW NL NO PL RO RU SD SE US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL SE BF BJ CF CG CI CM GA GN ML MR SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 2121235

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 1992921156

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 1994 211856

Country of ref document: US

Date of ref document: 19940727

Kind code of ref document: A

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWP Wipo information: published in national office

Ref document number: 1992921156

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 1992921156

Country of ref document: EP

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载