WO1985002411A1 - Lignee cellulaire et anticorps monoclonal - Google Patents

Lignee cellulaire et anticorps monoclonal Download PDF

Info

Publication number
WO1985002411A1
WO1985002411A1 PCT/AU1984/000237 AU8400237W WO8502411A1 WO 1985002411 A1 WO1985002411 A1 WO 1985002411A1 AU 8400237 W AU8400237 W AU 8400237W WO 8502411 A1 WO8502411 A1 WO 8502411A1
Authority
WO
WIPO (PCT)
Prior art keywords
breast
monoclonal antibody
antibody
carcinoma
antibodies
Prior art date
Application number
PCT/AU1984/000237
Other languages
English (en)
Inventor
Ian Farquhar Campbell Mckenzie
Original Assignee
The University Of Melbourne
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 The University Of Melbourne filed Critical The University Of Melbourne
Publication of WO1985002411A1 publication Critical patent/WO1985002411A1/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
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3015—Breast
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
    • A61K51/1045—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against animal or human tumor cells or tumor cell determinants
    • A61K51/1051—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against animal or human tumor cells or tumor cell determinants the tumor cell being from breast, e.g. the antibody being herceptin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2123/00—Preparations for testing in vivo

Definitions

  • TITLE CELL LINE AND MONOCLONAL ANTIBODY Background of the Invention
  • This invention relates to a new cell line and to monoclonal antibodies produced thereby.
  • the invention also relates to a method of detecting breast cancer using the antibodies embodying the invention.
  • Antibodies are primary components of immune defence systems and are made by the white blood cells (lymphocytes) in response to the presence of foreign material such as bacteria, virus, tumor cells or even inorganic chemicals. Such foreign material, known as antigens, are chemically highly i de nt i f ia bl e by means of the specific proteins produced thereby.
  • antibodies which are produced by the lymphocytes in response to the presence of antigens, are Y-shaped protein molecules, each of w h ic h can bind uniquely to the antigen and render same inert.
  • Mammalian antibody defence systems are highly flexible and it has b e e n estimated that the average person can make, a n t i b od ie s to more than a million different foreign molecules.
  • Familiar antibodies take the form of antiserums such as snake or spider venom antiserum. Other examples include anti-tetanus and anti-rabies antiserums, which are used in the treatment of such diseases.
  • antiserums are traditionally made by injecting forms of t.he various disease-carrying micro-organisms (the antigens) into domestic animals, such as rabbits, sheep, horses and goats.
  • the selective and specific binding capacity of antibodies has made them useful for another purpose - the detection of very small quantities of foreign molecules or antigens in blood, body fluids and tissues.
  • Antibodies have been used to diagnose disease since their discovery in the late 19th century, at first in relatively crude systems, but with increased sophistication until many millions of diagnostic tests are carried out annually at the time of writing. Until recently however the full potential of antibody-based diagnostic systems has not been realized.
  • Monoclonal antibodies are typically produced by using a cultured cancer cell (a myeloma) and a living cell taken from the spleen of a mammal (for example BALB/c strain of mouse).
  • a cultured cancer cell a myeloma
  • a living cell taken from the spleen of a mammal (for example BALB/c strain of mouse).
  • the spleen cell has already been primed with an antigen and is already producing a specific antibody.
  • the new cell thus formed is called a hybridoma.
  • the hybridoma displays the characteristics of both parent cells, in that it produces the same antibodies produced by the parent spleen cell and also exhibits the same vigorous growth, production and longevity characteristic of a cultured cancer cell.
  • Hybridomas formed by such fusions are cultured and cloned, and clones which produce antibodies demonstrating a specificity for a desired antigen are selected and cultivated. In this way, an ample supply of a monoclonal antibody specific to the antigen used to immunise or "prime" the parent spleen cell can be obtained.
  • the hybridoma is thus a highly sensitive diagnostic agent for the antigen in question. It is anticipated that the excellent specificity and ready availability of large quantities of monoclonal antibodies will cause a revolution in immunodiagnostic testing procedures within a relatively short time.
  • This invention provides a new cell line, which has been designated 3E1-2, which produces a monoclonal antibody having a predominant specificity to breast cancer antigens.
  • the invention also provides a monoclonal antibody having a predominant specificity to breast cancer antigens.
  • the invention also provides a method of detecting breast cancer in blood serum secretions or tissue comprising the step of applying to an immunoassay containing the blood serum, secretion or tissue to be tested a monoclonal antibody having a predominant specificity to breast cancer antigens and detecting the presence or absence of a reaction in said immunoassay.
  • the invention also provides for a continuous cell line identified as clone 3E1-2 which produces breast carcinoma antibodies in vitro in hypoxan th ine-aminopterin-thym idine medium comprising a fused cell hybrid of human adenocarcinoma-primed BALB/c mouse spleen cells, and NS-1 mouse myeloma cells, said antibodies reacting with a breast tissue antigen.
  • Figs. 1 and 2 are graphs showing the results of serum inhibition study conducted on a number of patients.
  • Monoclonal antibody 3E1-2 is produced against human carcinoma of the breast by the well-known method of immunizing BALB/c mice with breast cancer cells and performing a fusion of spleen cells from the immunised mouse with NS-1 myeloma cell line using polyethylene glycol as the fusing agent.
  • Antibody 3E1-2 is of the IgM class and is detected using an immunoperoxidase method to stain cancer of the breast cells.
  • Breast antigens are present in significantly greater than normal amounts in the blood serum, secretions or tissue of patients with carcinoma of the breast.
  • the antibody reacts very strongly with carcinoma of the breast antigens, and weakly or not at all with normal breast tissue.
  • the antibody the subject of this invention is uniformally negative with the surface of sime in vitro cancer cell lines. However, a 100% positive result has been found on breast cancer tissues. Some positive results were also derived from other cancer tissues such as lung or colon; however, the strength of the reaction was substantially less than the results derived from the breast cancer tissue. Positive reactions are obtained on formation fixed breast cancer tissue using the immunoperoxidase method so the antibody provides a useful reagent for histological diagnosis of breast cancer.
  • Antibody 3E1-2 therefore provides a highly satisfactory testing medium on tissue and blood serum for breast cancer using any suitable technique such as ELISA or radioi mmunoassay, both of which are well-known and require no further description. Since the antibody is effective in serum testing, one effect of the method of this invention is that it will be no longer necessary to physically remove tissue from the breast to test for cancer.
  • the test may be carried out on blood serum or other secretions and provides substantial savings in time and cost, as well as providing a simple diagnostic procedure suitable for general practitioners. Further, tests previously produced to test mammary tissue for breast cancer were notoriously unreliable. Lack of sensitivity and specificity often lead to false results, either positive, or regretably negative.
  • the method of the present invention provides results which are substantially more accurate.
  • one major feature of the invention lies in that a breast cancer test can be carried out using blood serum or other secretions as well as on tissue surgically removed from a suspect breast so that attractive alternatives to tissue testing are provided.
  • All human cell lines were maintained in RPMI-1640 medium containing 10% NCS, penicillin, streptomycin and glutamine.
  • the mouse myeloma P3-NSI-Ag4-1 (NS-1) was maintained in DMEM containing 10% NCS, penicillin, streptomycin and glutamine. (All media and additiives were obtained from Flow Laboratories, Sydney, Australia).
  • Adherent cell lines were harvested after the culture medium was decanted, and the cell monolayer exposed to 0.20% trypsin (commonwealth Serum Laboratories, Melbourne, Australia) at 37°C, for two minutes, followed by the addition of NCS to neutralize the trypsin.
  • Tissue sections (6um) were cut in a cryostat and placed on glass slides previously washed for two hours in 90% alcohol. Sections (5um) were also cut from formalin-fixed, paraffin embedded blocks and dried onto glass slides. The slides were rehydrated in xylene and alcohol, ready for the immunoperoxidase and immunofluorescence assays. Immunoperoxidase Staining After rehydration formalin-fixed tissue sections were treated with 0.5% H 2 O 2 in PBS for 30 minutes to remove endogenous peroxidase activity, then washed in PBS for 15 minutes (this step was omitted for fresh cryostat sections).
  • Tissue sections were covered with 1:10 dilution of supernatant containing antibody incubated in a humidified atmosphere for 40 minutes at room temperature, then washed for 15 minutes in PBS and 0.2% gelatin.
  • the slides were washed for 15 minutes in PBS and 0.2% gelatin, and then covered with a 1:20 dilution of swine anti-rabbit immunoglobul in antiserum conjugated with horse-radish peroxidase (DAKO- Immunoglobul ins, Copenhagen, Denmark) for 20 minutes.
  • DAKO- Immunoglobul ins horse-radish peroxidase
  • DAB di aminobenzi di ne
  • a monoclonal antibody directed against the Ly-2.1 antigen of the mouse lymphocyte was used as a non-reactive control and a medium control was also included for each experiment.
  • Immunofluorescence Tissue sections were stained by indirect immunofluorescence. Sections were incubated with a 1:10 dilution of the hybridoma culture supernatant for 40 minutes in a humidified atmosphere at room temperature.
  • the sections were subsequently washed in PBS, and stained with a sheep anti-mouse IgG antiserum conjugated with fluorescein. Stained sections were examined with a Leitz Orthoplan Fluorescene microscope by transmitted darkfield illumination with a narrow band blue excitation.
  • Immunoglobulin Assays The immunoglobulin isotype of the monoclonal antibody 3E1-2 was determined by Ouchterlony gel diffusion using class specific rabbit antisera to IgM, IgGl, IgG2a, IgG2b (Meloy Lab., Springfield, Va., USA).
  • the antibody titre of 3E1-2 was determined by subjectively examining histological sections (known positive sections) stained by antibody in dilution; the titer being recorded as the next and last tissue section which did not stain.
  • Serum Collection and Storage Samples of blood were obtained from patients with carcinoma of the breast, and normal female controls. Serum was separated by allowing the blood to clot, then spinning at 750g for 10 minutes. The serum was removed and stored at -70°C until use.
  • Kidney membrane was used as a source of antigen (as it is eadily available to us than breast tissue), preparations were made by taking 10° cells (cell lines or fresh tissue) and homogenising in 0.25M surcorse (25mM Tris, ImM EDTA, pH7.4) with a Dounce homogeniser at 4°C. The homogenate was spun at 2000g for one minute at 4°C to remove nuclei, and the resulting supernatant spun at 4,200 g for 10 minutes to pellet the crude membrane preparation and the portein content determined by the method described in 'Analytical Biochemistry' 1976 Vol 72 at pages 248 to 254.
  • the assay was performed by adding 50ul of a 200ug/ml stock solution of crude kidney membranes in PBS to a 96 well flexible PVC plate. Membranes were fixed to the plate with 50ul of 0.1% glutaraldehyde at room temperature for 15 minutes, washed in PBS, then treated with 100ul of 0.1M glycine for 15 minutes at room temperature to block free aldehyde groups. The wells were then washed twice with assay buffer (PBS + 0.5% BSA), then left in 100ul of buffer for 30 minutes at room temperature. Patients' serum (50ul) was added at the appropriate dilution, and to this 50ul of antibody 3E1-2 was added.
  • 3E1-2 was found to be of the IgM class and using the immunoperoxidase method on tissue sections had a titre on breast carcinoma cells of 1/2000 for supernatant and 1/20,000 for ascites. Reactivity of 3E1-2 with Breast Carcinoma The antigen detected by the 3E 1-2 antibody survived formalin-fixation and paraffin embedding, and so a large number of carcinomas of the breast, and normal tissues could be easily examined. Of the 37 carcinomas of the breast examined, all were positive for 3E1-2 (see Table 1).
  • Various types of breast carcinoma were represented and included 23 ductal carcinomas, 4 adenocarcinomas, 4 comedocarcinomas, 1 lobular carcinoma and 5 metastatic carcinomas. Of the 37 specimens examined, 31 had between 60-100% of malignant cells staining, 5 had 10-60% of malignant cells staining and one showed less than 10% of malignant cells staining. Although each histological type stained, the distribution of staining varied. Ductal carcinomas showed staining of both membranes and cytoplasm, whereas adenocareinoma exhibited predominantly luminal membrane staining and little cytoplasmic staining.
  • the immunoperoxidase technique revealed that 3E1-2 recognises an antigen present on normal breast tissue. However, it was restricted to only 60% of normal individuals tested, and on average, to 50% of ducts and acini in any one section. The staining was always of the liminal membrane surface, with the apical cytoplasm staining in some cases. This is in contrast to the pattern of staining seen in carcinoma of breast, where staining was cytoplasmic as well as membranous, with most sections showing greater than 80% of cells staining.
  • Benign lesions of the breast such as papilloma, gynaecomastia and fibroadenoma showed almost exclusively staining at the luminal membrane surface of neoplastic epithelial cells, a pattern similar to that of normal breast.
  • Cystic hyperplasia showed a staining pattern similar to the benign conditions.
  • Lobular hyperplasia however exhibited not only luminal membrane staining but also a staining of the epithelial cell cytoplasm, and of the myoepithelial cells.
  • a section of prelactating hyperplasia showed no staining of any hyperplastic components, whereas adjacent normal ducts in the same sections showed intense luminal membrane staining.
  • Tissues showing no staining were liver, prostate, ovary, spleen, colon, adrenal gland, parathyroid gland, bone marrow, gall bladder, cervix pancreas, lymph node, ileum, stomach, trachea, salivary gland, heart, lung, kidney, skin and thyroid.
  • Monoclonal antibody 3E1-2 was tested on a ranqe of non-breast tumours to further determine the distribution of the "antiqen” detected by the 3E1-2 antibody (Table 4). Using the immunoperoxidase technique it was found that 3E1-2 recognises an antigen present on renal, endometrial and cervical carcinomas.
  • carcinoma of colon malignant melanoma, nasopharyngeal carcinoma, basal cell carcinoma (skin), transitional carcinoma (urinary bladder), mucinous cystadenoma (ovary) and giant cell tumour of bone were found to be non-reactive with the 3E1-2 antibody.
  • Reactivity with in vitro cell lines An extensive range of in vitro cell lines were examined with the 3 El-2 antibody (Table 5). The antibody failed to react with 10/10 breast carcinoma cell lines, with 5/5 colon carcinoma cell lines, or to any other in vitro cell line, including cells derived from melanoma, and tumours of the uterus, lung, pancreas, kidney, parathyroid, and fibroblastic or haemopoietic derived cell lines.
  • T47D T47D, BT-20, PMC-42, MCF-7 - derived from carcinoma of the breast, PMC-115, PMC-116 - fibroblastic origin
  • T47D Staining of T47D was restricted to the inner cell membrane of 5% of cells, while 95% of BT-20 cells gave strong cytoplasmic staining.
  • Molecular Weight Estimation After cell surface labelling of fresh carcinoma of breast and normal kidney cells by both the lactoperoxidase and chloramine T methods, no specific bands were found on either 7.5% or 12.5% (reduced and unreduced) SDS-PAGE gels.
  • a r y carcinoma of breast and those with metastases showed significant inhibition of 3El-2 binding.
  • Fig. 2 shows diagramatically an example of this inhibition, comparing it to serum from a normal female control ( ⁇ standard deviation).
  • 3E1-2 detects an antigen present in serum, which is significantly raised in patients with carcinoma of the breast.
  • initial screening was performed on formalin fixed tissue, which led to the identification of an antigen which is resistant to formalin fixation and paraffin embedding.
  • this antigen also resists fixation by periodate-lysine-paraformaldehyde and glutaraldehyde, and as such, lends itself to conventional study by immunohistochemical means without having to resort to using fresh frozen tissue sections.
  • the nature of the epitope recognised by 3E1-2 is unknown, as is the molecule it resides on.
  • 3E1-2 recognises an antigen with a restricted distribution on normal human tissue. Indeed, 3E1-2 reacted predominantly with a subpopulation of epithelial cells. This phenomenon of antibodies recognizing epithelial "subsets" is not uncommon and has been previously reported for other monoclonal antibodies to human tumours.
  • the antigen is present on the surface membrane of breast, kidney and lung epithelium, and also on the membrane and cytoplasm of carcinomas derived from these tissue types. All of these tissues are involved in specialised secretory functions and one could postulate a role for the 3E1-2 molecule identified in that process. Compared to other monoclonal antibodies produced to carcinoma of the breast, 3E1-2 reacts with very few normal human tissues.
  • Cystic hyperplasia a "benign" change of the breast limited to fibrosis, sclerosing adenosis and cyst formation, shows luminal membrane and apical cytoplasmic staining, similar to that of normal and benign breast conditions.
  • lobular hyperplasia which is essentially an epitheliosis, showed not only luminal membrane staining but also cytoplasmic staining, and stain'ing of myoepithel ial cells. This finding is relevant in that only in the case of lobular hyperplasia is there evidence for transition to malignancy and carcinoma formation. Few carcinomas develop from fi broadenoma, gynaecomastia and fibrocystic disease.
  • 3E1-2 is localised to both the membrane and cytoplasm of malignant cells (Table 1).
  • the 3 ⁇ 1-2 antibody confirms the link between lobular hyperplasia and carcinoma of the breast, and may be important in studying the genesis of carcinoma of the breast.
  • 3E1-2 does not appear to recognise known components of human milk such as casien and lactalbumin, as immunoperoxidase staining of milk in histological sections was negative.
  • the distribution of immunoperoxidase staining and failure of SDS-PAGE analysis of breast tissue discounts hormone receptors for estrogen, progesterone and prolactin as the target.
  • the monoclonal anti-breast antibody used was 3E1-2 (IgM), which reacts strongly with membrane and cytoplasm of breast carcinomas and with the luminal membrane of normal breast.
  • Control monoclonal antibodies to murine antigens Thy-1.2 (IgM) and Ly-1.1 (IgG 11) were also used, and in several cases, the patients own IgG was isolated using protein A affinity chrom atography; an anti-colon carcinoma monoclonal antibody was also used: none of these control reagents reacted by the immunoperoxidase method with normal or malignant breast tissue.
  • the IgM antibodies were isolated from ascites fluid by dialysis against distilled water at 4°C after which the precipitate was collected; IgG antibodies by NH 4 (SO 4 ) 2 precipitation. Antibody activity measured either by the rosetting technique referred to above, or by the immunoperoxidase method on sections of breast carcinoma. The purified antibodies were retested for activity after all procedures, filtered through a 0.22um filter (Gelman Acrodisc, Michigan, USA), and tested for pyrogens,. and sterility prior to use. Radio Iodination
  • the currently available techniques for the detection of breast cancer include palpation, x-ray mammography, thermography, ultrasound, diaphranography and nuclear magnetic resonance.
  • these methods distinguish between benign and malignant lesions with difficulty. It is considered to be important to be able to detect metastases in draining axillary lymph nodes in carcinoma of the breast as this serves to distinguish the early and late stages of the disease and currently is used to design appropriate therapy.
  • the method of using radiolabelled monoclonal antibodies continued with scintography has recently been receiving some attention for the detection of a variety of tumours.
  • lymph nodes retained radiolabelled antibody both specifically (when involved with carcinoma of the breast) and non-specifically (when involved with other diseases such as lymphoma). This is not unexpected because of the greater vascularity of involved lymph nodes and because of the possibility of some hold up in lymphatics draining in these nodes.
  • immunoscintography described herein any different than lymphangiography using more conventional reagents. We feel the method does have advantages over the conventional lympha ⁇ giogram in that normal lymph nodes are not detected; there is twice as much (or more) specific antibody detected, compared with non-specific and in a grossly abnormal lymph node the collection of antibody was not greater than that found in other tissues.
  • rad io iodi nated antibody is not the best method for labelling because of the short half life in vivo of such antibodies.
  • tumours of 2.3mg could be detected and there is no reason why such a sensitivity should not be obtained in the type of studies described herein.
  • whether the method will approach that to detect micro-metastases in bone marrow will depend on the amount of antibody given, the quality and quantity of the radiolabel, and the detection system. Possibly the combined use of several antibodies to different epitopes on the cell surface may lead to a magnification and greater sensitivity.
  • stage 1 carcinoma localised to breast only
  • stage 2 histological-exam ination of axillary lymph nodes

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Cell Biology (AREA)
  • Oncology (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Biophysics (AREA)
  • Epidemiology (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • Optics & Photonics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Molecular Biology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

Lignée cellulaire produisant un anticorps monoclonal possédant une spécificité prédominante pour les antigènes du cancer du sein.
PCT/AU1984/000237 1983-11-25 1984-11-16 Lignee cellulaire et anticorps monoclonal WO1985002411A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AUPG2572 1983-11-25
AU257283 1983-11-25

Publications (1)

Publication Number Publication Date
WO1985002411A1 true WO1985002411A1 (fr) 1985-06-06

Family

ID=3693086

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/AU1984/000237 WO1985002411A1 (fr) 1983-11-25 1984-11-16 Lignee cellulaire et anticorps monoclonal

Country Status (3)

Country Link
EP (1) EP0162070A1 (fr)
IL (1) IL73620A0 (fr)
WO (1) WO1985002411A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0212403A2 (fr) * 1985-08-12 1987-03-04 Sloan-Kettering Institute For Cancer Research Anticorps monoclonaux contre des antigènes humains de différenciation du genre mucine
US4857452A (en) * 1986-12-04 1989-08-15 E. I. Du Pont De Nemours And Company Assay for carcinoma of breast, colon and ovary
US5849876A (en) * 1986-11-19 1998-12-15 Sanofi Hybridomas producing monoclonal antibodies to new mucin epitopes
US6004761A (en) * 1986-11-19 1999-12-21 Sanofi Method for detecting cancer using monoclonal antibodies to new mucin epitopes

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5894385A (ja) * 1981-11-30 1983-06-04 Asahi Chem Ind Co Ltd 細胞融合方法および細胞融合用試薬
AU1772983A (en) * 1982-05-21 1983-12-16 Regents Of The University Of California, The Human-human hybridomas for neoplasms
EP0118365A2 (fr) * 1983-03-04 1984-09-12 Health Research, Inc. Anticorps monoclonaux contre les cellules carcinomateuses mammaires humaines et leur application en diagnostic et en thérapie

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5894385A (ja) * 1981-11-30 1983-06-04 Asahi Chem Ind Co Ltd 細胞融合方法および細胞融合用試薬
AU1772983A (en) * 1982-05-21 1983-12-16 Regents Of The University Of California, The Human-human hybridomas for neoplasms
EP0118365A2 (fr) * 1983-03-04 1984-09-12 Health Research, Inc. Anticorps monoclonaux contre les cellules carcinomateuses mammaires humaines et leur application en diagnostic et en thérapie

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
KOHLER G., and MILSTEIN C., Nature, Vol. 256, August 7, 1975, pp. 495-497, "Continuous Cultures of Fused Cells Secreting Antibody of Predefined Specificity". *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0212403A2 (fr) * 1985-08-12 1987-03-04 Sloan-Kettering Institute For Cancer Research Anticorps monoclonaux contre des antigènes humains de différenciation du genre mucine
EP0212403A3 (fr) * 1985-08-12 1988-08-03 Sloan-Kettering Institute For Cancer Research Anticorps monoclonaux contre des antigènes humains de différenciation du genre mucine
US5849876A (en) * 1986-11-19 1998-12-15 Sanofi Hybridomas producing monoclonal antibodies to new mucin epitopes
US6004761A (en) * 1986-11-19 1999-12-21 Sanofi Method for detecting cancer using monoclonal antibodies to new mucin epitopes
US4857452A (en) * 1986-12-04 1989-08-15 E. I. Du Pont De Nemours And Company Assay for carcinoma of breast, colon and ovary

Also Published As

Publication number Publication date
EP0162070A1 (fr) 1985-11-27
IL73620A0 (en) 1985-02-28

Similar Documents

Publication Publication Date Title
JP3095752B2 (ja) Ｔａｇ‐７２及びヒト癌腫に対して結合特異性を有する第二世代モノクローナル抗体及びその使用方法
JP2660241B2 (ja) モノクロナール抗体
Stacker et al. A new breast carcinoma antigen defined by a monoclonal antibody
EP0201509A1 (fr) Anticorps monoclonal d'un antigene associe a une tumeur cancereuse chez l'homme.
US5153118A (en) Monoclonal antibodies having binding specificity to human prostate tumor-associated antigens and methods for employing the same
JPH08266273A (ja) 抗−ヒト乳癌モノクローナル抗体を産生するハイブリドーマ
JPH0249596A (ja) ヒト前立腺上皮細胞の表面に特異的に反応するモノクローナル抗体
JPS62220197A (ja) ヒト非小細胞肺癌および一定の他のヒト癌腫に対する単クロ−ン性抗体および抗原
EP0228243B1 (fr) Anticorps monoclonaux à spécificité de liaison contre les antigènes associés à des tumeurs humaines de la prostate
JPH0614873B2 (ja) モノクローナル抗体
US4585742A (en) Monoclonal antibody with specificity to human small cell carcinoma and use thereof
JPS61282096A (ja) 新規な腫瘍関連抗原
AU571287B2 (en) Cell line and monoclonal antibody
WO1985002411A1 (fr) Lignee cellulaire et anticorps monoclonal
Wikstrand et al. Production and characterization of two human glioma xenograft-localizing monoclonal antibodies
Carlson et al. Antigenic characterization of human hepatocellular carcinoma. Development of in vitro and in vivo immunoassays that use monoclonal antibodies.
US5250297A (en) Tumor-associated antigen, antibodies, compositions and uses therefor
JPS60208925A (ja) ガン診断と治療のためのモノクロ−ナル抗体の生産法
AU649613B2 (en) Monoclonal antibody for differentiation of squamous cell carcinoma antigens and method of use for same
JPH03188099A (ja) 新規な腫瘍関連抗原
EP0831895A1 (fr) Epitopes associes a une tumeur
AU640145B2 (en) A novel tumor associated antigen
JPH02219594A (ja) 肺癌に対するモノクローナル抗体および細胞表面抗原
AU625856B2 (en) Second generation monoclonal antibodies having binding specificity to tag-72 and human carcinomas and methods for employing the same
EP0242154A2 (fr) Antigène associé aux tumeurs

Legal Events

Date Code Title Description
AK Designated states

Designated state(s): AU FI JP US

AL Designated countries for regional patents

Designated state(s): AT BE CH DE FR GB LU NL SE