WO2004013317A1 - Procede permettant d'obtenir une souche de bacteriophages presentant une affinite accrue envers les cellules eucaryotes, preparations la contenant et utilisations de bacteriophages - Google Patents

Procede permettant d'obtenir une souche de bacteriophages presentant une affinite accrue envers les cellules eucaryotes, preparations la contenant et utilisations de bacteriophages Download PDF

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WO2004013317A1
WO2004013317A1 PCT/PL2003/000075 PL0300075W WO2004013317A1 WO 2004013317 A1 WO2004013317 A1 WO 2004013317A1 PL 0300075 W PL0300075 W PL 0300075W WO 2004013317 A1 WO2004013317 A1 WO 2004013317A1
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bacteriophage
bacteriophages
cell
cells
eukaryotic cell
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Krystyna Dabrowska
Andrzej Gorski
Anna Nasulewicz
Adam Opolski
Joanna Wietrzyk
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Instytut Immunologii I Terapii Doswiadczalnej Pan
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Publication of WO2004013317A1 publication Critical patent/WO2004013317A1/fr

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    • 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
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/76—Viruses; Subviral particles; Bacteriophages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
    • G01N33/57492—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites involving compounds localized on the membrane of tumor or cancer cells
    • 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
    • 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
    • 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
    • C12N2795/00—Bacteriophages
    • C12N2795/00011—Details
    • C12N2795/10011—Details dsDNA Bacteriophages
    • C12N2795/10111—Myoviridae
    • C12N2795/10132—Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
    • 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
    • C12N2795/00—Bacteriophages
    • C12N2795/00011—Details
    • C12N2795/10011—Details dsDNA Bacteriophages
    • C12N2795/10111—Myoviridae
    • C12N2795/10151—Methods of production or purification of viral material
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/005—Assays involving biological materials from specific organisms or of a specific nature from viruses

Definitions

  • the object of the invention is a method of obtaining bacteriophages of increased affinity to eukaryotic cells, novel applications of bacteriophages, a bacteriophage mutant, and pharmaceutical agents.
  • Neoplastic diseases present a serious challenge for contemporary medicine. Despite many years of research aimed toward achieving universal anti-tumor therapy, medicine does not possess the necessary tools for it. Therefore, there exists a need for agents and methods for the therapy, prevention and developmental arrest of neoplastic diseases.
  • Integrins comprise a large family of cell-surface receptors, expressed on a wide variety of cells (Giancotti, F. G., and Ruoslahti E.. (1999) Integrin Signaling. Science 285: 1028-1032; Arnaout, M. A., Goodman, S. L. and Xiong J. P. (2002) Coming to grips with integrin binding to ligands. Curr Opin Cell Biol 14: 641-651; Mousa, S. A. (2002) Anti-integrin as a novel drug-discovery targets: potential therapeutic and diagnostic implications. Curr Opin Chem Biol 6: 534-541).
  • Pancreas 25: 30-35 The integrin ⁇ llb ⁇ 3 is characteristic for the platelet, ligand binding to ⁇ llb ⁇ 3 is required for platelet aggregation (Basani, R. B., French D. L, Vilaire G., Brown D. L., Chen F., Coller B. S., et al. (2000) A naturally occurring mutation near the amino terminus of ⁇ u b defines a new region involved in ligand binding to ⁇ b ⁇ 3. Blood 95: 180-187).
  • Glanzmann's thrombasthenia is an exceptional, genetically heterogeneous syndrome associated with a bleeding tendency (D'Andrea, G., Colaizzo D., Vecchione G., Grandone E., Di Minno G., and Margaglione M. (2002) Glanzamann's thrombasthenia: identification of 19 new mutations in 30 patients. Thromb Haemost 87: 1034-1042).
  • a patient's platelets are characterized by a complete lack of aggregation due to a defect in the ⁇ llb ⁇ 3 complex or to a qualitative abnormality of this integrin expression (Belluci, S., and Caen J. (2002) Molecular basis of Glanzmann's thrombasthenia and current strategies in treatment. Blood Rev 16: 193-202).
  • the goal of this invention is to provide a method of obtaining bacteriophages displaying an affinity to eukaryotic cells.
  • Bacteriophages possessing an increased affinity to eukaryotic cells may find an array of applications in both therapy and diagnostics. What is desired in this specific instance is to obtain bacteriophages of increased affinity to tumor cells.
  • the goal of the invention is, in particular, to provide agents which may be employed in the diagnosis, treatment, prevention and developmental arrest of diseases connected with the appearance of cells defined as eukaryotic, particularly neoplastic ones.
  • An object of the invention is a method of obtaining a strain of bacteriophages of increased affinity to eukaryotic cells, this method being characterized in that it comprises steps, in which (a) the eukaryotic cell comes in contact with bacteriophages, (b) unbound or weakly bound bacteriophages are removed, and (c) the bacteriophage bound to the eukaryotic cell multiplies within a bacterial cell, thereby achieving a strain of bacteriophage of increased affinity to the eukaryotic cells.
  • step (a) additionally include subjecting the bacteriophages to the activity of a mutagenic agent before contact with the eukaryotic cell.
  • the eukaryotic cell be a neoplastic cell.
  • step (a) It is advisable to incubate the eukaryotic cells of step (a) with a solution containing bacteriophages at a ratio of 1 to 10 5 pfu bacteriophages to 1 eukaryotic cell, by which it is more advantageous to incubate the eukaryotic cells of step (a) with a bacteriophage solution at a ratio of 1000 pfu bacteriophages to 1 eukaryotic cell at a temperature of 37°C for 2 hours. It is advisable that in step (b) of the method according to the invention at least one cell rinsing be carried out, more advisable being 1 to 10 cell rinsings in step (b) with water or a low-concentration saline solution.
  • step (c) of the method according to the invention it is advisable in step (c) of the method according to the invention that the bacteriophage culture be conducted using the two-layer plate method. It is advisable in step (c) of the method according to the invention that the cell suspension containing bacteriophages obtained from the multiplication process be passed through an antibacterial filter.
  • An object of the invention is also bacteriophage strain of increased affinity to eukaryotic cells obtainable in process accoding to the invention. Further aspect of the invention is the bacteriophage possessing the identifying characteristics of strain HAPl deposited at Polish Collection of Microorganisms (PCM) under deposit No. F/00028. An object of the invention is also the application of a bacteriophage to bind to a eukaryotic cell, advantageously a tumor cell.
  • An object of the invention is also the application of a bacteriophage which binds to a eukaryotic cell to produce preparations for the diagnosis and/or treatment and/or prevention and/or developmental arrest of diseases connected with the appearance of this eukaryotic cell, advantageously when the eukaryotic cell is a neoplastic cell.
  • An object of the invention is also an preparation for the diagnosis and/or treatment and/or prevention and/or developmental arrest of diseases connected with the appearance of a eukaryotic cell, this agent or drug being characterized in that its active agent contains a bacteriophage which binds with the eukaryotic cell, advantageously a neoplastic cell.
  • the said preparation may contain at least one bacteriophage strain according to the invention, as defined above.
  • Therapeutic applications may include targeted therapy, consisting of, for example, using bacteriophages as drug delivery agents (e.g. an exogenous protein built into its structure, or exogenous, therapeutic DNA built into the genome of the bacteriophage).
  • drug delivery agents e.g. an exogenous protein built into its structure, or exogenous, therapeutic DNA built into the genome of the bacteriophage.
  • Another therapeutic application of the bacteriophages obtained may consist of indirect stimulation and directing of the immune response of the host organism to a tissue to which the bacteriophage displays affinity.
  • Bacteriophages of increased affinity to neoplasm may be employed in the treatment, prevention and developmental arrest of neoplastic diseases as well as in the prevention of the onset of metastases.
  • the figures provided represent a supplemental part of this description.
  • Figure 1 presents the number of tumor colonies in the lungs of mice 22 days after intravenous administration of B16 mouse melanoma cells to the amount of 3 x 10 5 cells/mouse.
  • the mice of the group T4 were given the T4 bacteriophage lysate, the HAPl mice the HAPl bacteriophage lysate, the SON mice bacteria which had been disrupted by ultrasound, while the mice of the control group K received a physiological salt solution (for a detailed description, see Example 2 below).
  • Figure 2 presents the ability of bacteriophage T4 to bind (A) the lymphocytes T and (B) the platelets isolated from blood of patient with Glanzmann's thrombasthenia and healthy person.
  • Figure 3 presents bacteriophages bounded to melanoma cell membranes - visualized in electron micrographs, bacteriophages were marked with arrows, B16 cells - melanoma cell, B16 cells + T4 phage - melanoma cell after incubation with bacteriophage T4, B16 cells + HAPl phage - melanoma cells after incubation with bacteriophage HAP 1.
  • Figure 4 presents labelled bacteriophages bounded to melanoma cell membranes - visualized in confocal microscopy, a- B16 melanoma cells after incubation with labelled bacteriophage T4, b - B16 melanoma cells after incubation with labelled bacteriophage HAPl.
  • Figure 5 presents antimetastatic effect of purified bacteriophages T4 and HAPl in nude (athymic) mice (4-8 x 10 7 pfu/mouse), N - number of mice inoculated with B16 melanoma cells, saline - mice treated with 0.9% NaCl (control), T4 - mice treated with bacteriophage T4 (1 dose 1 hour before inoculation with B16 and 21 subsequent daily doses), HAPl - mice treated with bacteriophage HAPl (1 dose 1 hour before inoculation with B16 and 21 subsequent daily doses)- statistically significant to control (p ⁇ 0.05)
  • Example 1 Obtaining a bacteriophage mutant of increased affinity to eukaryotic cells.
  • B16 mouse melanoma transplant cells were used as the target cells. This cell line was obtained from the National Cancer Institute, Bethesda, MD, U.S.A., and is currently kept at the Cell Line Bank of the Department of Tumor Immunology of the Institute of Immunology and Experimental Therapy (IITD) , Wroclaw, Tru.
  • the T4 bacteriophage was purchased from the American Type Culture Collection, U.S.A.
  • the bacteriophage lysates were produced from culturing the bacteriophage on Escherichia coli B bacteria from the Collection of Microorganisms of the IITD. The lysates were passed through a 0.22 ⁇ m Millipore antibacterial filter. The bacteriophage lysate titers used in the experiments were 10 8 - 10 9 pfu/ml. Mutagenesis of the T4 bacteriophage was carried out using EMS (ethyl methane sulfonate, Sigma) [Lawley P.D., Martin C.N. (1975): Molecular Mechanisms in Alkylation Mutagenesis. Biochem. J. 145, 85-91].
  • EMS ethyl methane sulfonate
  • a series of passes of the bacteriophage on the B16 cells was conducted in vitro.
  • the B16 cells were incubated with the bacteriophage lysate at a ratio of 1000 pfu T4 bacteriophages to 1 B16 cell at a temperature of 37°C for 2 hours.
  • the B16 cells were rinsed 5 to 7 times with 0.9% NaCl: the cells were centrifuged, the supernatant was poured off, and the cells were suspended in the 0.9% NaCl.
  • the final cell suspension was used to culture bacteriophages by the two-layer plate method [Adams M.H. (1959): Bacteriophages. Inter.
  • the lysate of the T4 bacteriophage and the lysate obtained after PPF culture on Escherichia coli B bacteria from the Collection of Microorganisms of the IITD were prepared in such a way that the titers of both lysates were the same.
  • the lysates were passed through a 0.22 ⁇ m Millipore antibacterial filter. B16 cells with the above lysates were incubated at a ratio of 1000 pfu bacteriophages to 1 B16 cell at 37°C for 2 hours.
  • the B16 cells were rinsed seven times with 0.9% NaCl: the cells were centrifuged, the supernatant was poured off, and the cells were suspended in the 0.9% NaCl.
  • the number of cells in the final cell suspension was determined as well as the bacteriophage titer.
  • the bacteriophage titer was also determined in the last supernatant poured off in order to verify the removal of unbound bacteriophages.
  • the ratio of bacteriophages to cells in the final B16 cell suspension was determined. It was confirmed that this ratio was higher in the case of B16 cells incubated in lysate won by way of PPF culturing than that of B16 cells incubated with T4 bacteriophages (Table 1).
  • bacteriophages obtained by PPF were cultured from single plaques.
  • the cultures were done on Escherichia coli B bacteria from the Collection of Microorganisms of the IITD in such a way that the titers in the lysates were the same.
  • the lysates were passed through a 0.22 ⁇ m Millipore antibacterial filter.
  • For each pure phage line thus obtained its ability to bind with B16 cells was compared with that of the T4 bacteriophage (conducted as above).
  • the bacteriophage line displaying the greatest difference from the T4 bacteriophage was selected and received the designation HAPl (Tab. 2).
  • the HAPl bacteriophage was deposited at the Polish Collection of Microorganisms (PCM) with the access number F/000028 on August 5, 2002, in accordance with the requirements of the Budapest Treaty.
  • PCM Polish Collection of Microorganisms
  • Form BP 9 (second and last page) Table 1. Comparison ofthe binding ability ofthe T4 bacteriophage to B16 cells with that ofthe bacteriophage population obtained by way of passage selection (PPF)
  • bacteriophages can display affinity to eukaryotic cells. Moreover, it was unexpectedly discovered that the method presented allows obtaining bacteriophages of increased affinity to eukaryotic cells, for example tumor cells.
  • CB was 29 and 16 (for B 16 and HS294T, respectively) while CB of T4 was 4 and 2 (for B 16 and
  • BP T4 and HAPl binding of B16 melanoma cells in vitro was also visualized by electron microscopy.
  • BPs were incubated with B16 cells (109 pfu per 106 cells, 2 hours, 37°C), the sample was centrifuged (10 min, 1000 rpm, 20°C, a minimal acceleration) and the supernatant was discarded. Both bacteriophages could be detected at the cell surface, attached (or very close) to its membrane (fig.3).
  • SYBR I green fluorescent dye
  • Example 2 The anti-tumor activity of bacteriophages which bind to tumor cells.
  • B16 mouse melanoma transplant cells were used in the study. This cell line was obtained from the National Cancer Institute, Bathesda, MD, U.S.A. and is now on deposit at the Cell Line Bank ofthe Department of Tumor Immunology ofthe IITD.
  • a cell suspension derived from in vitro culture was used to transplant the cells intravenously (i. v.).
  • a similar suspension of cells (3xl0 5 /mouse) in a solution of 0.9% NaCl at a volume of 0.2 ml was injected into the lateral tail vein.
  • we achieve "experimental" (artificial) metastasis [compare: Technical considerations for studying cancer metastasis in vivo. Clin Exp Metastasis 1997; 15: 272-306].
  • part ofthe tumor cells survive in the circulation and, after lingering in and then leaving the vascular lumen, homes in on the organ in which it can create tumor foci. In the case of B16 melanoma, this organ is the lung.
  • T4 bacteriophage purchased from the American Type Culture Collection, U.S.A., and a substrain of it, HAPl, which is characterized by an increased affinity to B16 melanoma cells and selected by way of serial passes in vitro of T4 bacteriophage on B16 melanoma cells (see Example 1), were used.
  • Bacteriophage lysates obtained from culturing bacteriophages on Escherichia coli B bacteria from the Collection of Microorganisms of the IITD were used. The lysates were passed through a 0.22 ⁇ m Millipore antibacterial filter before injection into the animals.
  • the titers of the bacteriophage lysates were 1 - 2 x 10 9 pfu/ml.
  • Animals of the first control group were given a 0.9% NaCl solution, those ofthe second control group Escherichia coli B bacteria from the Collection of Microorganisms of the IITD after the bacteria had been disrupted ultrasonically and passed through a 0.22um Millipore antibacterial filter.
  • Gas chromatography-mass spectrometry (GC-MS) was used to compare the lipopolysaccharide (LPS) content ofthe lysates and ultrasonically disrupted bacteria, and samples containing the same amounts of LPS were prepared.
  • LPS lipopolysaccharide
  • mice of the study group T4 were given the T4 bacteriophage lysate, of the group HAPl the HAPl bacteriophage lysate, ofthe control group SON the ultrasonically disrupted bacteria, and ofthe control group K a physiological salt solution.
  • the first dose was administered 1 hour before the introduction of tumor cells, and subsequent doses once a day, beginning 24 hours after the introduction ofthe tumor cells, until the end of the experiment, i.e. for 21 to 22 days.
  • the animals were observed over a period of 3 weeks. The mice were then sacrificed by dislocation of the cervical vertebrae and the particular organs examined in detail.
  • bacteriophage preparations especially the one containing the HAPl phage of increased affinity to B16 cells, proved to retard the formation and metastasis of tumors in the lungs of animals which had been injected intravenously with neoplastic cells. This attests to a great therapeutic potential of bacteriophage preparations possessing an affinity to eukaryotic cells which cause disease.
  • the ⁇ llb ⁇ 3 integrin is the most abundand platelet cell-surface receptor and ligand binding to ⁇ llb ⁇ 3 is required for platelet aggregation (Basani, R. B. et al. A naturally occurring mutation near the amino terminus of allb defines a new region involved in ligand binding to ⁇ llb ⁇ 3.
  • Glanzmann's thrombasthenia is an exceptional, genetically heterogeneous syndrome associated with a bleeding tendency (D'Andrea, G.
  • Glanzamann's thrombasthenia identification of 19 new mutations in 30 patients. Thromb. Haemost. 87, 1034-42 (2002)).
  • Such patient's platelets are characterized by a complete lack of aggregation due to a defect in the allbb3 complex or to a qualitative abnormality of this integrin expression (Belluci, S. & Caen, J. Molecular basis of Glanzmann's thrombasthenia and current strategies in treatment. Blood Rev. 16, 193-202 (2002)).
  • the patient's platelets were isolated from blood (Method described by: HM Dick, WB Crichton (1972): Tissue Typing Techniqes 1072:page 52).
  • the patient's T-lymphocytes were isolated from blood (Method described by: Jerzak M., Baranowski W., Rechberger T., G ⁇ rski A.(2002), Immunol Lett., 2002 A ⁇ rl;81(l):65-70) and activated by incubation with phorbol myristate acetate (10 ng/ml, 10-20 min. 220C).
  • Bacteriophage lysate was incubated with platelets or T-lymphocytes suspensions (10 pfu per 10 platelets, 1 hour, 37°C and 10 6 pfu per 10 6 lymphocytes, 1 hour, 37°C), centrifuged ( for platelets: 30 min, 4500 rpm, 10°C, a minimal acceleration; for lymphocytes 7min, 1300rpm, 4°C, a minimal acceleration). The phage concentration in the supernatant was measured. The results are presented in on figure 2.
  • KGD-containing peptide and both anti- ⁇ v ⁇ 3 and anti- ⁇ llb ⁇ 3 antibodies although an effect of anti- ⁇ llb ⁇ 3 antibody was weaker than that of anti- ⁇ v ⁇ 3 (tab.4).
  • Irrelevant antibody and irrelevant (non-RGD non-KGD) peptide caused no effect on cell-phage binding.
  • HAPl - bacteriophage HAPl lysate KGD - peptide with a KGD-like motif (IntegrilinTM)
  • Example 5 Antimetastatic effect of purified bacteriophages T4 and HAPl in B16 melanoma model in nude mice.

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Abstract

Selon la présente invention, les bactériophages présentant une affinité envers les cellules eucaryotes servent au diagnostic et/ou au traitement et/ou à la prévention et/ou à arrêter le développement de maladies associées à l'apparition de cellules eucaryotes, en particulier de cellules néoplasiques.
PCT/PL2003/000075 2002-08-05 2003-08-05 Procede permettant d'obtenir une souche de bacteriophages presentant une affinite accrue envers les cellules eucaryotes, preparations la contenant et utilisations de bacteriophages WO2004013317A1 (fr)

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PL355355A PL195815B1 (pl) 2002-08-05 2002-08-05 Sposób otrzymywania szczepu bakteriofaga o zwiększonym powinowactwie do komórek eukariotycznych, środki go zawierające i zastosowania bakteriofagów
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1618886A1 (fr) * 2004-07-20 2006-01-25 Fonds zur Förderung der Forschung auf dem Gebiet der molekularen Virologie und Gentherapie Protéines de bactériophages and prophages dans la thérapie génique du cancer
WO2006066224A2 (fr) * 2004-12-14 2006-06-22 Yale University Antibiotiques ciblés contre un facteur de virulence
WO2014195871A1 (fr) * 2013-06-03 2014-12-11 Warszawski Uniwersytet Medyczny Utilisation de bactériophages

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL212286B1 (pl) 2010-06-20 2012-09-28 Inst Immunologii I Terapii Doswiadczalnej Pan Sposób otrzymywania bakteriofagów

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996021007A2 (fr) * 1994-12-30 1996-07-11 Chiron Viagene, Inc. Systemes de transfert genique a mediation par bacteriophage capables d'effectuer une transfection des cellules eucaryotiques

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996021007A2 (fr) * 1994-12-30 1996-07-11 Chiron Viagene, Inc. Systemes de transfert genique a mediation par bacteriophage capables d'effectuer une transfection des cellules eucaryotiques

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
PEREIRA S ET AL: "A model system for detection and isolation of a tumor cell surface antigen using antibody phage display", JOURNAL OF IMMUNOLOGICAL METHODS, ELSEVIER SCIENCE PUBLISHERS B.V.,AMSTERDAM, NL, vol. 203, no. 1, 1997, pages 11 - 24, XP004058767, ISSN: 0022-1759 *
POUL M-A ET AL: "Targeted gene delivery to mammalian cells by filamentous bacteriophage", JOURNAL OF MOLECULAR BIOLOGY, LONDON, GB, vol. 288, no. 2, 30 April 1999 (1999-04-30), pages 203 - 211, XP004455923, ISSN: 0022-2836 *
SWITALA-JELEN K ET AL: "Mutations in bacteriophage T4 genome", ACTA VIROLOGICA, vol. 46, no. 2, 2002, pages 57 - 62, XP008025059, ISSN: 0001-723X *
TOPPING KATHERINE P ET AL: "Isolation of human colorectal tumour reactive antibodies using phage display technology", INTERNATIONAL JOURNAL OF ONCOLOGY, vol. 16, no. 1, January 2000 (2000-01-01), pages 187 - 195, XP008025070, ISSN: 1019-6439 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1618886A1 (fr) * 2004-07-20 2006-01-25 Fonds zur Förderung der Forschung auf dem Gebiet der molekularen Virologie und Gentherapie Protéines de bactériophages and prophages dans la thérapie génique du cancer
WO2006008312A1 (fr) * 2004-07-20 2006-01-26 Austrianova Biotechnology Gmbh Proteines bacteriophages et prophages dans la therapie genique anticancereuse
WO2006066224A2 (fr) * 2004-12-14 2006-06-22 Yale University Antibiotiques ciblés contre un facteur de virulence
WO2006066224A3 (fr) * 2004-12-14 2007-03-29 Univ Yale Antibiotiques ciblés contre un facteur de virulence
WO2014195871A1 (fr) * 2013-06-03 2014-12-11 Warszawski Uniwersytet Medyczny Utilisation de bactériophages
US9850467B2 (en) 2013-06-03 2017-12-26 Warszawski Uniwersytet Medyczny Methods of using T4 bacteriophage in treatment of adenoviral infections caused by HAdV-5

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