DE2835272A1 - Prodn. of mouse immunoglobulin-E antibodies - by generating and growing an immunoglobulin-E producing hybrid cell line - Google Patents

Prodn. of mouse immunoglobulin-E antibodies - by generating and growing an immunoglobulin-E producing hybrid cell line

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DE2835272A1
DE2835272A1 DE19782835272 DE2835272A DE2835272A1 DE 2835272 A1 DE2835272 A1 DE 2835272A1 DE 19782835272 DE19782835272 DE 19782835272 DE 2835272 A DE2835272 A DE 2835272A DE 2835272 A1 DE2835272 A1 DE 2835272A1
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cell line
antibodies
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Irmgard Boettcher
Joachim-Friedrich Dr Kapp
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Bayer Pharma AG
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Schering AG
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Priority to AT79102797T priority patent/ATE1387T1/en
Priority to DE7979102797T priority patent/DE2963410D1/en
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    • 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
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/10—Cells modified by introduction of foreign genetic material
    • C12N5/12—Fused cells, e.g. hybridomas
    • C12N5/16—Animal cells
    • C12N5/163—Animal cells one of the fusion partners being a B or a T lymphocyte
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    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/44—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, amino acids
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    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
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Abstract

Prodn. of mouse IgE antibodies is carried out by (a) generating an IgE-producing hybrid cell line (specifically the new IgE-14-205 cell line) in known manner, and (b) isolating the IgE antibody after growth of the cells. The IgE antibody obtd. from the IgE-14-205 cell line is a well-defined substance with reproducible allergen-specificity w.r.t. ovalbumin. It is free of other types of antibody and can be produced in large amt., making it useful for generating standardised allergic reactions for testing antiallergic agents.

Description

Die Erfindung betrifft ein Verfahren zur Herstellung bzw. Gewinnung vonThe invention relates to a method for production or extraction from

ImmunglobulinE (IgE)-Antikörpern der Maus, mit denken sich an Versuchstieren spezifisch und-reprodusierbar Allergien erzeugen lassen.Immunoglobulin E (IgE) antibodies of the mouse, with think of laboratory animals Allow specific and re-modifiable allergies to be generated.

Nachdem es K.Ishizaka et al. EJ.Immunol. 97, 75 (1966)g gelang, IgE-Antikörper als Vermittler allergischer Reaktionen zu identifizieren, bemühte man sich verstärkt, diesen neuen Typ von Immunoglobulinen aus dem Serum allergischer Tiere bzw. allergischer Patienten zu isolieren.After K.Ishizaka et al. EJ.Immunol. 97, 75 (1966) g succeeded, IgE antibodies to identify as a mediator of allergic reactions, efforts were made to this new type of immunoglobulins from the serum of allergic animals or allergic animals Isolate patient.

Diese Allergien-vermittelnden Antikörper treten jedoch in derartig geringen Konzentrationen auf, daß zunächst alle Versuche einer Isolierung scheiterten. S.G.O. Johansson et al. tImmunology 13, 381 C196?)J und später H. Bazin et al. SJ.Nat Gancer Inst. 51, 1359 (1975) identifizierten äußerst selten spontan auftretende IgE-produzierende Myelome bei Mensch und Ratte Eine allergenische Spezifität dieser IgE-Hyelom-Proteine konnte bisher nicht nachgewiesen werden.However, these allergy-mediating antibodies occur in such a way low concentrations that initially all attempts at isolation failed. S.G.O. Johansson et al. tImmunology 13, 381 C196?) J and later H. Bazin et al. SJ.Nat Gancer Inst. 51, 1359 (1975) identified extremely rarely occurring spontaneously IgE-producing myelomas in humans and rats An allergenic specificity of these IgE hyeloma proteins could not be detected so far.

Für Untersuchungen über den Ursprung und Mechanismus allergischer Prozesse wäre ein IgE-Antikörper mit reproduzierbarer Allergen-Spezifität ebenso von Bedeutung wie für die Auffindung von antiallergisch wirksamen Substanzen.For studies of the origin and mechanism of allergic Processes would be an IgE antibody with reproducible allergen specificity as well of importance as well as for the discovery of antiallergic substances.

Die Erfindung betrifft auch eine neue murine Zellinie (IgE-14-205), mit der man kontinuierlich große Mengen von IgE-Antikörpern mit Antiovalbumin (OA)-Spezifität herstellen kann. Diese neue murine Zellinie wird durch Zellfusion zwischen murinen Myclomzellen~ und Milzzellen von OA-hyperimmunisierten Mäusen in an sich bekannter Weise hergestellt. Durch die neue Zellinie ist es erstmals möglich, größere Mengen von Maus-IgE zur Verfügung zu stellen, was bisher stets mit erheblichen Schwierigkeiten verbunden war. Das mit Hilfe der neuen Zellinie hergestellte IgE ist der erste anwendbare Antikörper,der eine homogene Antigenspezifität besitzt und damit sich besonders zur Auslösung standardisierter allergischer Reaktionen eignet. Darüber hinaus eignet er sich aufgrund seiner Homogenität hervorragend als Agenz für die verschiedensten immunochemischen, pathophysiologischen, immungenetischen und pharmakologischen Studien zur Aufklärung des Mechanismus allergischer Reaktionen. In der tierexperimentellen Forschung versteht man unter Versuchstieren alle zu Testzwecken in Frage kommenden Tierspezies. Besonders geeignet für die Auffindung antiallergisch wirksamer Verbindungen sind Maus und Ratte, an denen die durch das erfindungsgemäße Verfahren hergestellten IgE-Antikörper in Verbindung mit dem spezifischen Antigen Ovalbumin reproduzierbare allergische Reaktionen erzeugen können.The invention also relates to a new murine cell line (IgE-14-205), with which one continuously large amounts of IgE antibodies with antiovalbumin (OA) specificity can produce. This new murine cell line is created by cell fusion between murine Mycloma cells and spleen cells from OA-hyperimmunized mice are known per se Way made. Through the new cell line it is possible for the first time to make larger amounts of mouse IgE available, which has always been considerable so far Difficulty was associated. The IgE produced with the help of the new cell line is the first applicable antibody that has a homogeneous antigen specificity and therefore particularly suitable for triggering standardized allergic reactions suitable. In addition, due to its homogeneity, it is ideal as a Agent for a wide variety of immunochemical, pathophysiological, immunogenetic and pharmacological studies to elucidate the mechanism of allergic reactions. In animal research, laboratory animals are understood to be all for test purposes eligible animal species. Particularly suitable for finding antiallergic more effective compounds are mouse and rat, on which the by the invention Procedure produced IgE antibodies in association with the specific antigen Ovalbumin can produce reproducible allergic reactions.

Die Erfindung wird im folgenden näher erläutert.The invention is explained in more detail below.

1. HERSTELLUNG DER HYBRID-ZELLINIE IgE-14-205 Zur Zellfusionierung verwendet wurden 1. die permanent in vitro wachsende 8-Azaguanin-resistente murine Myelomsellinie P 3-X63-Ag 8 (Köhler, G. and Milstein, C. Nature 256, 495, 1975) 2. Milzzellen aus Ovalbumin-hyperimmunisierten Balb/c-Häusen (Hyperimmunisierung nach Kulczycki et al., J. exp. Med. 139, 600, 1974) Die Milzzellen wurden 3-7 Tage nach der letzten Ovalbumin-Immunisierung mit den Myelomzellen P 3-X63-Ag 8 in Gegenwart von 42 % Polyäthylenglykol für 1-2 Minuten bei 370C fusioniert (Hämmerling, G.J., Eur. J. Immunol. 7, 743, 1977). Durch ZAT-Selektion (Littlefield, J.W., Science 145, 709, 1964) wurden Hybridzellinien gewonnen, deren Zellkulturiib erstände 3-5 Wochen nach der Zellfusion im passiven cutanen Anaphylaxietest (PCA) der Ratte (Ovary, Z., Immunological Methods, et. J.F. Ackroyd, Blackwell Scientific Publ., Oxford, 1964, S.259) auf IgE-anti-Ovalbumin-Antikörperproduktion getestet wurden. Nach Auffindung einer IgE-Antikörper synthetisierenden Bybridzellinie wurde durch mehrfache Subclonierung die monoclonale Hybridzellinie IgE-14-205 hergestellt.1. PREPARATION OF THE HYBRID CELL LINE IgE-14-205 For cell fusion 1. the 8-azaguanine-resistant murine, which is permanently growing in vitro, was used Myeloma line P 3-X63-Ag 8 (Köhler, G. and Milstein, C. Nature 256, 495, 1975) 2. Spleen cells from ovalbumin-hyperimmunized Balb / c houses (hyperimmunization according to Kulczycki et al., J. exp. Med. 139, 600, 1974) The spleen cells were 3-7 days after the last ovalbumin immunization with the myeloma cells P 3-X63-Ag 8 in the presence fused from 42% polyethylene glycol for 1-2 minutes at 370C (Hämmerling, G.J., Eur. J. Immunol. 7, 743, 1977). By ZAT selection (Littlefield, J.W., Science 145, 709, 1964) hybrid cell lines were obtained, the cell cultures of which were obtained 3-5 Weeks after cell fusion in the passive cutaneous anaphylaxis test (PCA) of the rat (ovary, Z., Immunological Methods, et. J.F. Ackroyd, Blackwell Scientific Publ., Oxford, 1964, p.259) were tested for IgE anti-ovalbumin antibody production. After discovery a hybrid cell line synthesizing IgE antibodies was obtained by multiple subcloning produced the hybrid monoclonal cell line IgE-14-205.

2. IgE-PRODUKTION DURCH DIE EYBRID-ZELLINIE IgE-14-205 2.1 Die Hybridzellinie IgE-14-205 synthetisiert permanent in der Zellkultur (z.B. als Suspensionskultur in DMEM- oder RPMI 1640-Medium) Maus IgE-anti-Ovalbumin-Antikörper, die in das Zellkulturmedium sezerniert werden.2. IgE PRODUCTION BY THE EYBRID CELL LINE IgE-14-205 2.1 The hybrid cell line IgE-14-205 is permanently synthesized in cell culture (e.g. as a suspension culture in DMEM or RPMI 1640 medium) mouse IgE anti-ovalbumin antibodies that are in the cell culture medium to be secreted.

2.2 Die Hybridzellinie IgE-14-205 wächst auch als subcutaner oder intraperitonealer Tumor speziesspezifisch in Balb/c-Mäusen und produziert unter diesen in vivo-Bedingungen große Mengen des IgE-Antikörpers, die aus dem Serum und Ascites der tumortragenden Tiere gewonnen werden können (Tab. 1). 2.2 The hybrid cell line IgE-14-205 also grows as subcutaneous or intraperitoneal tumor species-specific in Balb / c mice and produced under these in vivo conditions large amounts of the IgE antibody that are obtained from the serum and Ascites from tumor-bearing animals can be obtained (Tab. 1).

Tab. 1 Wachstum der Hybridzellinie IgE-14-205 als Tumor in der Balb/c-Maus Quantitativer Nachweis der durch den Tumor produzierten IgE-Antikörper in Serum und Ascites der tumortragenden Mäuse durch den PCA-Test. Der PCA-Titer ist als reziproker Wert der höchsten Serum- bzw. Tab. 1 Growth of the hybrid cell line IgE-14-205 as a tumor in the Balb / c mouse Quantitative detection of the IgE antibodies produced by the tumor in serum and ascites of the tumor-bearing mice by the PCA test. The PCA titer is more than reciprocal Value of the highest serum resp.

Ascitesverdünnung angegeben, der eine allergische Hautreaktion erzeugt. Ascites thinning indicated, which creates an allergic skin reaction.

IgE-14-205- Tage nach Tumor- PCA-Titer Applikation Applika- rate Serum Ascites tion subcutan 8 5/5 8 kein Asc. IgE-14-205 days after tumor PCA titer application rate of application Serum ascites subcutaneous 8 5/5 8 no Asc.

18 5/5 1024 " ll intraperito- 8 4/5 32 1? -neal 18 6/6 50000 131000 3. ISOLIERUNG DES MURINEN IgE-ANTI-OVALBUMIN-ANTIKÖRPERS DER HYBRIDZELLINIE IgE-14-205 3.1 Isolierung des IgE-Antikörpers aus dem Zellkulturüberstand der in Zellkultur wachsenden Hybridzellinie IgE-14-205 über folgende Reinigungsschritte: 1. Fraktionierte (NH4)2So4-FällUng 2. DEAE-Chromatographie mit linearem NaCl- Gradient 3. Sephacryl G200-Gelfiltration Ausbeute: Einige mg hochgereinigtes biologisch aktives IgE aus 1 1 Zellkulturüberstand. 18 5/5 1024 "ll intraperito- 8 4/5 32 1? -Neal 18 6/6 50,000 131,000 3. ISOLATION OF MURINE IgE ANTI-OVALBUMIN ANTIBODY OF HYBRID CELL LINE IgE-14-205 3.1 Isolation of the IgE antibody from the cell culture supernatant in the cell culture growing hybrid cell line IgE-14-205 via the following purification steps: 1. Fractionated (NH4) 2So4 precipitation 2. DEAE chromatography with linear NaCl gradient 3. Sephacryl G200 gel filtration Yield: A few mg of highly purified biologically active IgE from 1 1 cell culture supernatant.

3.2 Isolierung des IgE-Antikörpers aus dem Serum und Ascites der IgE-14-205-Tumor-tragenden Maus.3.2 Isolation of the IgE antibody from the serum and ascites of the IgE-14-205 tumor-bearing Mouse.

Verfahren gemäß 3.1. Procedure according to 3.1.

Ausbeute: einige mg hochgereinigtes biologisch aktives IgE aus 10 - 20 ml Serum bzw. Ascites. Yield: a few mg of highly purified biologically active IgE from 10 - 20 ml of serum or ascites.

4. CHARAKTERISIERUNG DES IgE-ANTI-OVALBUMINlANTIKÖRPERS AUS DER HYBRIDZELLINIE IgE-14-205 4.1 Das Molekulargewicht des gereinigten IgE-Antikörpers beträgt -> 200.000 daltons (Bestimmung durch Sepharose Gelilektrophorese in Gegenwart von Molekulargewichtsmarkern).4. CHARACTERIZATION OF THE IgE ANTI-OVALBUMIN ANTIBODY FROM THE HYBRID CELL LINE IgE-14-205 4.1 The molecular weight of the purified IgE antibody is -> 200,000 daltons (determined by Sepharose gel electrophoresis in the presence of molecular weight markers).

4.2 Der IgE-14-205-Antikörper zeigt die für IgE-Immunglobuline typische Hitzelabilität: 2 h 560 C führen zur biologischen Inaktivierung des Antikörpers (Nachweis im PCA-Test) (s. Tab. 2).4.2 The IgE-14-205 antibody shows that which is typical for IgE immunoglobulins Heat stability: 2 hours at 560 C lead to biological inactivation of the antibody (Proof in the PCA test) (see Tab. 2).

4.3 Der IgE-14-205-Antikörper besitzt Allergenspezifität.4.3 The IgE-14-205 antibody has allergen specificity.

Der IgE-14-205-Antikörper löst eine allergische Reaktion, z. B. die PCA-Reaktion nur in Verbindung mit dem spezifischen Allergen (Ovalbumin) aus, sie unterbleibt, wenn Ovalbumin weggelassen oder durch ein anderes Protein, z. B. Rinderserumalbumin (BSA) ersetzt wird (s. Tab. 2). The IgE-14-205 antibody triggers an allergic reaction, e.g. B. the PCA reaction only in connection with the specific allergen (ovalbumin) from them omitted if ovalbumin is omitted or replaced by another protein, e.g. B. Bovine Serum Albumin (BSA) is replaced (see Tab. 2).

Tab. 2 Charakterisierung des IgE-14-205-Antikörpers IgE-Antikörper ADergen PCA-Reaktion 1. IgE-14-205 OA + 1. IgE-14-2O5 OA + 2. IgE-14-205,hitze- OA inaktiviert (2 h, 56° C) 3. IgE-14-205 4. - OA 5. IgE-14-205 BSA 4.4 Der IgE-14-205-Antikörper zeigt die für Maus-Immunglobulin E typische heterologe Reaktion mit Rattenmastzellen. Er löst in der Ratte in Verbindung mit den spezifischen Allergen allergische Reaktionen aus, z. B. erzeugt der murine IgE-14-205-Antikörper in der Ratte eine passive cutane (PCA) und passive peritoneale Anaphylaxie (PPA) (Tab. 3).Tab. 2 Characterization of the IgE-14-205 antibody IgE antibodies ADergen PCA reaction 1. IgE-14-205 OA + 1. IgE-14-2O5 OA + 2. IgE-14-205, heat- OA inactivated (2 h, 56 ° C) 3. IgE-14-205 4. - OA 5. IgE-14-205 BSA 4.4 The IgE-14-205 antibody shows the heterologous reaction with rat mast cells typical of mouse immunoglobulin E. In connection with the specific allergen, it triggers allergic reactions in rats off, e.g. B. the murine IgE-14-205 antibody produces a passive cutaneous in the rat (PCA) and passive peritoneal anaphylaxis (PPA) (Table 3).

Tab. 3 Passive peritoneale Anaphylaxie der Ratte, ausgelöst durch den Antikörper IgE-14-205 Versuchsgruppe Tierzahl allergischer Histamin-Release IU) Kontrolle mit IgE- 8 1,58+0,31 100 14-205 Kontrolle ohne IgE- 9 0,57+0,05 0 14-205 5 mg/kg DSCG 5 0,74+0,19 17 Wistar-Ratten erhielten i.p. 2 ml 1:5 verdünnten Ascites aus IgE-14-205-tumortragenden Mäusen (PCA-Titer 3000).Tab. 3 Passive peritoneal anaphylaxis in the rat, triggered by the antibody IgE-14-205 test group number of animals allergic histamine release IU) Control with IgE- 8 1.58 + 0.31 100 14-205 Control without IgE- 9 0.57 + 0.05 0 14-205 5 mg / kg DSCG 5 0.74 + 0.19 17 Wistar rats received i.p. 2 ml 1: 5 diluted ascites from IgE-14-205 tumor-bearing mice (PCA titer 3000).

Nach 2 Stunden wurde die allergische Reaktion durch i.v.-Injektion von OA ausgelöst und die allergische Histaminfreisetzung aus den peritonealen Mastzellen spektrofluorimetrisch bestimmt (IU=spetrofluorimetrische Intensitätseinheiten). Hemmung des allergischen Histamin-Release durch 5 mg/kg Disodiumcromoglycat (DSCG, IntalR), i.p.After 2 hours the allergic reaction was stopped by IV injection triggered by OA and the allergic histamine release from the peritoneal mast cells Determined spectrofluorimetrically (IU = spetrofluorimetric intensity units). Inhibition of the allergic histamine release by 5 mg / kg disodium cromoglycate (DSCG, IntalR), i.p.

verabreicht direkt vor der OA-Applikation.administered directly before the OA application.

5. VERWEIJDUNG DES IgE-14-205-ANTIKÖRPERS ZUR TESTUNG ANTIALLERGISCH WIRKSAMER UERBINDWiGEN Gegenüber den für experimentell erzeugte allergische Reaktionen bisher verwendeten durch Hyperimmunisierung hergestellten IgE-haltigen Immunseren bietet der Einsatz des Antikörpers IgE-1-205 folgende Vorteile: 5.1 Der IgE-14-205-Antikörper ist monoclonal u. ermöglicht deshalb jederzeit die Induktion qualitativ und quantitativ reproduzierbarer allergischer Reaktionen.5. DENY OF IgE-14-205 ANTIBODY FOR TESTING ANTIALLERGIC MORE EFFECTIVE BINDING Compared to those for experimentally generated allergic reactions previously used IgE-containing immune sera produced by hyperimmunization the use of the antibody IgE-1-205 offers the following advantages: 5.1 The IgE-14-205 antibody is monoclonal and therefore enables induction qualitatively and quantitatively at any time reproducible allergic reactions.

5.2 Der IgE-14-205-anti-OA-Antikörper ist im Gegensatz zu IgE-haltigen Immunseren frei von Antikörpern anderer Immunglobulinklassen mit gleicher Allergenspezifität (z.B. IgG-anti-OA).5.2 The IgE-14-205 anti-OA antibody is in contrast to IgE-containing antibodies Immune sera free of antibodies from other immunoglobulin classes with the same allergen specificity (e.g. IgG anti-OA).

5.3 Der IgE-14-205-anti-OA-Antikörper ist im Gegensatz zu IgE-haltigen Immunseren frei von IgE-Antikörpern mit unbekannter Allergenspezifität.5.3 The IgE-14-205 anti-OA antibody is in contrast to IgE-containing antibodies Immune sera free of IgE antibodies with unknown allergen specificity.

Der IgE-14-205-Antikörper eignet sich deshalb besonders zur Testung antiallergisch wirksamer Verbindungen, deren Wirkstärke quantitativ reproduzierbar ermittelt werden muß. Tab. 3 zeigt als Beispiel die Hemmung der durch den IgE-14-205-Antikörper ausgelösten passiven peritonealen Anaphylaxie der Ratte durch Disodiumcromoglycat (Intal ).The IgE-14-205 antibody is therefore particularly suitable for testing antiallergic compounds whose potency is quantitatively reproducible must be determined. Tab. 3 shows, as an example, the inhibition of the by the IgE-14-205 antibody Passive peritoneal anaphylaxis induced in rats by disodium cromoglycate (Intal).

Claims (5)

Verfahren zur Gewinnung von ImmunglobulinE-Antikörern der Maus mit bekannter Allergenspezifität-Patentansj>rüche 1) Verfahren zur Gewinnung von ImmunglobulinE-(IgE)-Antikörpern der Maus, dadurch gekennzeichnet, daß man in an sich bekannter Weise eine IgE-Antikörper-produzierende Hybrid-Zellinie herstellt und nach Wachstum die IgE-Antikörper isoliert.Method for obtaining immunoglobulin E antibodies from mice known allergen specificity patent claims 1) Method for obtaining ImmunoglobulinE (IgE) antibodies of the mouse, characterized in that one in is known to produce an IgE antibody-producing hybrid cell line and after growth, the IgE antibodies are isolated. 2) Verfahren nach Anspruch 1, dadurch gekennzeichnet, daß man die IgE-Antikörper-produzierende Hybrid-Zellinie IgE-14-205 herstellt 2) Method according to claim 1, characterized in that the IgE antibody-producing hybrid cell line IgE-14-205 3) Verfahren nach Anspruch 2, dadurch gekennzeichnet, daß man die Hybrid-Zellinie IgE-14-205 in Suspensionskultur wachsen läßt.3) Procedure according to Claim 2, characterized in that the hybrid cell line IgE-14-205 is in suspension culture lets grow. 4) Verfahren nach Anspruch 2, dadurch gekennzeichnet, daß man die Hybrid-Zellinie als IgE-produaierenden Tumor in der Maus wachsen läßt.4) Method according to claim 2, characterized in that the Hybrid cell line grows as IgE-producing tumor in the mouse. 5) Verwendung von aus der Hybrid-Zellinie IgS-14-205 gewonnenen ImmunglobulinE-Antikörpern der Maus zur Auffindung von antiallergisch wirkenden Verbindungen, dadurch gekennzeichnet, daß man an Versuchstieren spezifisch und reproduzierbar Allergien erzeugen kann.5) Use of immunoglobulin E antibodies obtained from the hybrid cell line IgS-14-205 the mouse to find antiallergic compounds, characterized in that that one can specifically and reproducibly produce allergies in test animals.
DE19782835272 1978-08-10 1978-08-10 Prodn. of mouse immunoglobulin-E antibodies - by generating and growing an immunoglobulin-E producing hybrid cell line Pending DE2835272A1 (en)

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Application Number Priority Date Filing Date Title
DE19782835272 DE2835272A1 (en) 1978-08-10 1978-08-10 Prodn. of mouse immunoglobulin-E antibodies - by generating and growing an immunoglobulin-E producing hybrid cell line
EP79102797A EP0008092B1 (en) 1978-08-10 1979-08-03 Process for obtaining murine immunglobulin-e antibodies, hybrid cell lines used in the process and the process for preparing them, application of the immunglobulin-e antibodies so obtained
AT79102797T ATE1387T1 (en) 1978-08-10 1979-08-03 METHODS FOR OBTAINING MOUSE IMMUNOGLOBULIN ANTI-BODIES, THE HYBRID CELL LINES SUITABLE THEREFORE AND THEIR PRODUCTION; USE OF THE IMMUNOGLOBULIN E ANTIBODIES SO OBTAINED.
DE7979102797T DE2963410D1 (en) 1978-08-10 1979-08-03 Process for obtaining murine immunglobulin-e antibodies, hybrid cell lines used in the process and the process for preparing them, application of the immunglobulin-e antibodies so obtained

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