JPH08504088A - Tumor-specific antibodies and antigens - Google Patents

Abstract

  (57) [Summary] The present invention relates to a novel epitope of 180,000 daltons for the NCAM antigen and monoclonal antibodies against this antigen, SEN7, and their use in the diagnosis and treatment of small cell carcinoma of the lung. The antibody SEN7 reacts with cells of small cell carcinoma of the lung with significantly greater selectivity than already known antibodies and binds with high affinity. In particular, it does not react with white blood cells and healthy kidney or lung epithelial cells. The novel antigen is predominantly expressed by small copy number cells of the lung in high copy number.

Description

DETAILED DESCRIPTION OF THE INVENTION Tumor-Specific Antibodies and Antigens The present invention relates to novel tumor antigens, antibodies to this antigen and their use in the diagnosis and treatment of small cell carcinoma of the lung. Small cell carcinoma of the lung tends to form early metastases. For this reason, surgical, radiological or chemotherapeutic treatment is often only an interim treatment. Upon regression, the resistance to previously effective treatments, such as radiation and chemotherapy, manifests itself in complications. For this reason, it has been considered in the future to provide specific post-therapy with antibodies or antigen-conjugated active substances to patients after conventional treatment of primary tumors. Labeled antibodies may also be used for demonstration of metastases by imaging or for examination of tumor tissue by histological techniques. Many antigens are known that are expressed by cells of small cell carcinoma of the lung. Experts' Agreement (First and Second International Workshop on Lung Cancer Antigens, Brit. J. Cancer, 63 (Suppl.), 10-19, 1991 and J. Nat. Cancer Inst. , 83 , 609-612, 1991), they are divided into 7 groups. Antibodies against these antigens are also known. In animal models, these antibodies have sometimes been used for local localization of tumor cells. Important known antigens of small cell carcinoma of the lung include neural cell adhesion molecules (neural cell adhesion molecule, NCAM) and cluster 2 and w4 antigens. Others include Mucin and Lewis ^y There are antigens and ABO blood group antigens. Antibodies to NCAM and the cluster w4 antigen also bind leukocytes. Antigens to the cluster 2 antigen also bind epithelial tissue. This makes this type of antibody desirable for immunological tumor therapy but unsuitable for systemic application. The high affinity for a particular antigen is even more useful because the antibody is highly concentrated in tumor tissue. The antigens found to date and antibodies to these antigens with relative specificity for cells of small cell carcinoma of the lung are not sufficiently selective. The detection of cells of small cell carcinoma of the lung using these is not sufficiently reliable. The specificity of already known tumor antigens and the affinity of already known antibodies are also unsuitable for the method of immunological treatment of this disease. The object of the present invention is to provide novel tumor antigens of this carcinoma and antibodies against these antigens in order to facilitate the diagnosis and treatment of small cell carcinoma of the lung. In particular, the aim is to provide an antigen in which multiple copies are predominantly expressed, preferably only in tumors. Antibodies to this type of antigen should be distinguished by their high affinity. A novel cell surface antigen of small cell carcinoma of the lung has now been found, which is significantly more specific than already known antigens of tumor cells and does not occur especially on leukocytes or healthy kidney or lung epithelial cells Has been characterized. The novel antigen is predominantly expressed in multiple copy numbers by cells of small cell carcinoma of the lung. The present invention provides a monoclonal antibody that specifically binds to a novel antigen with a strong affinity. Thus, the present invention provides a murine monoclonal antibody designated SEN7, as well as SEN7.2a. Which secretes monoclonal antibody SEN7. No. 4 and the deposit number DSM ACC 2050. The invention further relates to a humanized antibody which has a murine hypervariable region and a human framework grooved region and a constant region and which comprises the hypervariable region from the monoclonal antibody SEN7. The invention also relates to an antigen, in particular of human origin, from cells of a small cell carcinoma of the lung, characterized in that it is bound by the antibody SEN7. The present invention also particularly relates to a conjugate with a toxin, a radioisotope and / or a labeling agent, which comprises a humanized antibody having an antibody SEN7 or a hypervariable region of the antibody SEN7 as an antibody component. Concerning the conjugate. The invention further relates to a humanized antibody having antibody SEN7 or a hypervariable region of antibody SEN7 and / or an antibody conjugate comprising antibody SEN7 as an antibody component or a humanized antibody having a hypervariable region of antibody SEN7, which has a small lung size. Use for the production of a preparation for the treatment and / or diagnosis of cell carcinoma. The invention further relates to a humanized antibody having antibody SEN7 or a hypervariable region of antibody SEN7 and / or an antibody conjugate comprising antibody SEN7 as an antibody component or a humanized antibody having a hypervariable region of antibody SEN7, which has a small lung size. Use for the treatment and / or diagnosis of cell carcinoma. Ordinarily, monoclonal antibodies can be obtained from soybean cells, especially mouse cells. These antibodies produce an unwanted immune response for in vivo use in humans. To avoid these unwanted immune reactions, antibodies intended for in vivo use in humans are modified so that they no longer recognize them as foreign. Common modification methods for these purposes include CDR grafting (Janes, PT., Et al, Nature. 321 , 14-17, 1986 and Kettle-borough, CA, et al, Prot ein Engineering. Four , 773-783, 1991). Further possible modifications are known to the person skilled in the art. This type of modified antibody is referred to as a humanized antibody in the present invention. These are linked to labeling substances (tracers) in order to allow the analytical detection of antibodies. For example, the antibody can be labeled with a radioactive isotope. For these purposes, the radioactive isotopes of yttrium, rhenium and technetium, especially I125 and I131, and also In111 are commonly used. Methods of isotope labeling and other radioisotopes suitable for labeling are known to those of skill in the art. In addition to these radiolabels, additional non-isotopic labels are well known to those of skill in the art. These are often preferred in analytical work. For example, it is also possible to label with a fluorescent substance such as fluorescein or an enzyme such as peroxidase or alkaline phosphatase instead. Selection of the appropriate fluorophore or enzyme and the required detection methods are known to those skilled in the art. In many cases, it is more convenient to not bind the labeling substance directly to the antibody, but indirectly with an additional strong binding ligand. Biotin / avidin or biotin / streptavidin combinations have proven to be particularly suitable for this purpose. The choice of this type of ligand and the required binding methods are known to those skilled in the art. In the present invention, corresponding to these examples, the term labeling substance should be understood to mean both the labeling substance used in the direct labeling method and the combination used in the indirect labeling method including the binding ligand. . Depending on the immunotherapy, the biological effects of the antibody are directly utilized. In other immunological therapies, compounds intended to damage the diseased tissue are additionally or sometimes exclusively used. This injury can be brought about, for example, by the radioactivity of isotopes such as I131 or I125, or by cytotoxic agents including plant or bacterial toxins such as ricin A or gelonin and cytostatics. Further suitable radioisotopes and cytotoxic agents are known to those skilled in the art. All these substances are designated in the present invention by the term toxin. Antibodies carry toxins to sites of action, such as tumors, where they destroy diseased cells. Mice were immunized with experiments to prepare the antigen of the invention and antibodies to this antigen. As the immunogen, cells of small cell carcinoma of the lung that had been previously treated with neuraminidase were used. Cells of the human cell line SW2 were used specifically for this purpose. While examining the resulting murine monoclonal antibody, a cell line secreting an antibody of isotype IgG1 was found, which was designated SEN7. This antibody reacted with all lung small cell carcinoma cell lines examined (15). No reaction was observed in the lung monolayer cell carcinoma (3) and lung adenomas (3) cell lines. It was revealed that this antibody is specific to a previously unknown epitope of the neural cell adhesion molecule (NCAM) and does not belong to any of the known groups. Cell lines secreting the antibody SEN7 are SEN7.2a. 4 has been deposited with the German Microbial and Cell Culture Collection (Brunswick, Germany) (Deposit No. DSM ACC2050). The characteristics of the novel epitope of the NCAM molecule recognized by the monoclonal antibody SEN7 are described below. The antibody SEN7 is also characterized. Further experimental details are given in the examples. Standard biochemical methods for the production and isolation of antibodies, the characterization of antibodies and antigens and the induction of radioisotopes are known to those of skill in the art, eg Antibodies, a Laboratory Manua (Harlow and Lane (eds), Cold. Spring Harbor Laboratory, 1988) and other reference books and reviews. The usual variants are also described in this. For immunization of mice (BALB / c), small cell carcinoma cells of the lung (cell line SW 2) were treated with neuraminidase. For details of this type of method and suitable immunization regimens, see, eg, Int. J. Ccancer, 35 , 11-17, 1985 and Cancer Research 48 , 412-417, 1988) and others known to those skilled in the art. The cell line P3X63Ag8.653 was used as the fusion partner. The fused cells were cultured, cloned, and the clones were cultured again. The antibodies produced were examined on untreated and neuraminidase treated SW 2 cells using indirect immunofluorescence. Cell lines in which the antibody did not react with cells from bone marrow or leukocytes were further selected. The binding of the antibody to the cells can be detected using a fluorescently labeled secondary antibody. The antibody SEN7 thus isolated was classified by type and found to belong to the IgG1 isotype. The SEN7 producing cells were cultured in the hollow fiber system. The antibody was purified from the culture supernatant by affinity chromatography on a Protein A column. Western blot analysis was performed to characterize the antigen recognized by antibody SEN7. The cell line OH3, which is derived from a small cell carcinoma of the lung and reacts with the antibody SEN7, was used as the antigen source. Cell surface antigens were each extracted by detergent treatment in the presence of a mixture of various protease inhibitors. The extracts were separated by known methods using electrophoresis on polyacrylamide gels in the presence of sodium dodecyl sulfate. The fraction thus separated did not react with the antibody SEN7. For this purpose, the separated fractions were first reconstituted (regenerated) with urea by known methods. A clear protein band with a molecular weight of 180,000 daltons was seen after this treatment. This band was present under non-reducing conditions with the cell lines SW2 and OH3. This was not present in the negative control without the primary antibody. To further characterize the antigen, SW2 cells were cultured in the presence of tunicamycin. In this process, the nitrogen-binding carbohydrate biosynthesis is inhibited. FACScan analysis of this type of cultured cells showed that they did not react with the antibody SEN7. Thus, the epitope bound by antibody SEN7 comprises an asparagine-linked oligosaccharide. The antigen is therefore a glycoprotein. To perform antibody characterization, serial dilutions of SW2 cells were treated with isotope-labeled antibody. The free and cell-bound antibody content was then determined by radioactivity measurement. Data analysis revealed that the antibody had an affinity constant, K _a = 2 x 10 ⁹ M ^-1 Binding, indicating that there are approximately 200,000 binding sites per cell. To determine the binding specificity of antibody SEN7, live cells of various carcinomas were examined by indirect immunofluorescence. The reaction was positive in all 16 cell lines of small cell carcinoma of the lungs examined. No staining was observed in three cell lines (U1752, HOTZ and LX1, squamous cell carcinoma or anaplastic carcinoma of the lung). The same applies to the three cell lines examined further (A125, SLC52 and Λ549, adenocarcinoma). Examination of white blood cells and peripheral blood lymphocytes showed that the antibody did not bind to these cells. Furthermore, it was confirmed that hemagglutination did not cause binding to red blood cells. In contrast to the known antibodies that react non-selectively with leukocytes and lymphocytes against the antigen group cluster 1 and cluster w4, the antibodies according to the invention do not react with these cells. The epitope of NCAM according to the invention is thus not present on the surface of these cells. Tissue samples of tumor and healthy tissues were further examined by known immunoperoxidase staining. Small cell carcinomas or carcinomas of the lung showed a positive reaction (6 of 7 samples and 2 of 3 samples, respectively). All other tumor tissues examined (adenocarcinoma, breast cancer, colon cancer, renal carcinoma and lymphoma) did not respond. Individual cell types reacted positively in healthy thyroid gland, adrenal gland, muscle, testis, peripheral nerves, spinal cord, brain and pituitary tissue. Healthy tissue reactions from skin, bronchi, lungs, kidneys, liver, large intestine, lymph nodes and pancreas were completely negative. Antibody distribution was determined in mice with xenografts as a model system for imaging and therapeutic use. For this, 107 washed cells of the cell line SW2 were each injected subcutaneously into mice. The examination was started as soon as the tumor reached a weight of approximately 100 mg. At this point, an equal amount of SEN7 antibody ( ¹²⁵ I-labeled) and MG-1 antibody as a control ( ¹³¹ The mixture was injected into animals. Like the antibody SE N7, the control antibody belongs to the class IgG1. The organ distribution of the two antibodies was examined over several days. The antibody was absorbed by the tumor from the blood circulation. That is, after the third day, the antibody SEN7 at a concentration 3-5 times higher than that in blood was measured in the tumor. This absorption was specific. That is, the concentration in the liver (non-specific decomposition reaction site) was as low as 15 to 20 times lower than the concentration in the tumor. The injected dose was at most 32%, based on the weight of the organ. Without further elaboration, one of ordinary skill in the art will be able to utilize the invention to the full extent using the above description. Therefore, the preferred specific embodiments are for purposes of illustration only and are not intended to limit the disclosure in any way. The complete disclosure of all applications, patents and publications and corresponding applications cited above and below, German DE 42 31 066, received September 17, 1992 and 43 14 870, received May 5, 1993, are incorporated by reference. Attach here. Examples The following abbreviations are used. PBS : Phosphate buffered saline solution (137 mM NaCl, 2.7 mM KCl, 8 mM Na2HP0 _Four , 1.5 mM KH ₂ PO _Four ) BSA : Bovine serum alpmin TCA : Trichloroacetic acid DMSO : Dimethyl sulfoxide DMF : Dimethylformamide TBS buffer : Tris buffer containing 1 M NaCl (50 mM, pH 7.3) Unless otherwise stated, cultures of hybridoma cell lines are based on RPMI1640 medium with the following additives. That is, 10% (v / v) fetal bovine serum, 10% (v / v) supplemented H1 (BM-Condimed®, Boehringer Mannheim), 1% (v / v) L-glutamine and 1%. (V / v) insulin-oxaloacetate-pyruvate solution (1.5 mg cis-oxaloacetate, 0.5 g sodium pyruvate and 2000 units of insulin are added to 80 ml of ice, then HCl becomes clear. (PH 3-4) and bring the solution to 100 ml with water). Incubation is performed at room temperature (RT: 15 to 28 ° C) unless otherwise specified. Example 1 Hybridoma cell line secreting antibody SEN7 SEN7.2a. Preparation of 4 Mice (BALB / c) were immunized with Stahel RA, et al, Int. J. Cancer 35 , 1 1-17, 1985. Cells of small cell carcinoma of the lung (cell line SW2, Dana Farber Institute, Boston, Massachusetts, USA) are treated with neuraminidase from C. perfringens (2 hours at 37 ° C, 1 enzyme unit of neuraminidase / 10). ⁶ cell). After immunization, further treatment is performed by the method described in the above document. Cells of cell line P3X63-Ag8.653 are used as fusion partners. The fused cells are cultured, cloned, and the clones are cultured again. The antibodies produced are examined by indirect immunofluorescence for binding of untreated and neuraminidase treated SW2 cells. Select cell lines in which the antibody does not react with cells from bone marrow or white blood cells. 2x10 for immunofluorescence ^Five Individual cells (tumor, bone marrow or blood cells) were dispensed into test tubes, respectively, in 10 μl of PBS2 with 0.1% sodium azide. ^-7 Incubate with M test antibody for 1 hour at 4 ° C. The cells are washed, treated with 50 μl of a solution containing fluorescein-labeled anti-mouse antibody (goat) and washed again. The binding of antibody to cells can be detected by fluorescence. The antibody thus isolated is called SEN7. It belongs to the isotype IgG1 / κ, as shown by tests with a test stick (Amersham, UK). Example 2 Production and purification of antibody SEN7 Cell line SEN7.2a. Four cells are cultured in RPMI 1640 medium supplemented with 10% (v / v) fetal bovine serum and 2 mM L-glutamine in the hollow fiber system (Axist, Technomara, Switzerland). Antibodies are adsorbed from the culture supernatant on a Protein A column (BIO-RAD, Richmond, CA, USA). For this, the culture supernatant is subjected to a column in 50 mM Tris-HCl (pH 8.9) containing 3.3 M NaC1 and then 50 mM Tris-HCl (pH 8.3) containing 3.3 M NaCl until the eluate is protein free. Wash in 9). The bound IgG antibody is eluted with 50 mM sodium acetate buffer (pH 6.0) containing 150 mM NaCl. The eluate is dialyzed against 25 mM sodium acetate buffer (pH 5.5), applied to an ion exchange column (Mono-S®, Pharmacia, Uppsala, Sweden) and eluted with a NaCl gradient. The antibody preparation thus obtained was proven to be homogeneous by SDS-PAGE and isoelectric focusing. [Example 3] Isotope labeling of antibody SEN7 ¹²⁵ For labeling with I, 40 μg of IodoGen® (Pierce, UK) is dissolved in 50 μl of chloroform. The solution is concentrated to dryness in a 1.5 ml container. 50 μl PBS solution of 100 μg SEN7 antibody and 200 μCi ¹²⁵ A solution containing I-iodide is added to this vessel. The reaction mixture is stirred for 5 minutes. The reaction is then stopped by adding 50 μl of tyrosine (Fluka) saturated PBS solution. A column packed with SEPHADEX® G-25 is equilibrated with PBS solution of BSA (10 g / l) and used for separation of iodine not bound to protein. The radiochemical purity of the labeled protein determined by TCA precipitation is above 95%. Iodine isotope ¹³¹ I is similarly introduced. The same reaction is used for the preparation of radiolabeled derivatives of other antibodies (eg MG-1). Example 4 Western Blot Analysis of SEN7 Antigen Western blot analysis is performed to isolate the antigen recognized by the antibody SEN7. The cell line OH3, which is derived from a small cell carcinoma of the lung and reacts with the antibody SEN7, is used as the antigen source. 10 ⁷ Cells were treated with 45 mM 3-[(3-colamidopropyl) dimethylammonio] propanesulfonate (CHAPS) and 0.1% NaN. ₃ And a mixture of various protease inhibitors (0.1 mM 1,10-phenanthroline, 0.1 mM 3,4-dichloroisocoumarin, 0.05 mM N- [N- (L-3-trans-carboxylane-2 -Carbonyl) -L-leucyl] agmatine (E-64), 50 μg / ml pepstatin A and 0.1 mg / ml calpain inhibitor peptide) and extracted in PBS for 1 hour at 0 ° C. For this, the suspension is mixed briefly on a vortex mixer. The extracts are then freed of cell debris by centrifugation (1 hour, 100,000 xg). Extracts are separated by polyacrylamide gel (7.5%) electrophoresis in O'Farrel buffer system in the presence of sodium dodecyl sulfate. The gel is regenerated in 6M, 3M and 1.5M urea, then in water and migration buffer (pH 10.5, 10M 3- [cyclohexylamino] -1-propanesulfonic acid, 10% methanol) for 30 minutes each. Let The proteins are then electrophoretically transferred to Immun-Lite P membranes (BioRGG, CH) at 100 Vh. Membranes from Johnson, DA. et al, Gene Anal. Tech., 1 , 328-334, 1984) and pretreated with 50 g / I skim milk powder in PBS, and then 10 ^-7 Incubate with affinity purified SEN7 at a concentration of M overnight at 4 ° C. Unbound antibody is washed away with 0.5 g / l Tween 20 in PBS. The gel is treated with goat anti-mouse IgG solution conjugated with alkaline phosphatase. After washing, bands are visualized on X-ray film by incubation with luminescent material. A single protein band with a molecular weight of 180,000 is seen. For the cell line OH3, this band is present under non-reducing conditions. This is not seen in the negative control without primary antibody. Example 5 Determination of SEN7 Binding Constants Serial dilutions of SW2 cells were made up to 10 with 100 μl of PBS containing 1% bovine serum albumin and 0.1% sodium azide. ⁷ Prepare starting from individual cells. Each dilution is treated with 40 ng of the isotope-labeled antibody according to Example 3 for 2 hours at 4 ° C. The cells are then centrifuged and the amount of free and cell-bound antibody determined by measuring radioactivity. The data show that the antibody has an affinity constant K _a = 2 x 10 ⁹ M ^-1 Binding and that there are approximately 200,000 binding sites per cell. Example 6 Reaction of antibody SEN7 with NCAM-transfected cells The reaction of antibody SEN7 was investigated in cells that had been transfected with complementary DNA. This cDNA encodes an isoform of human NCAM (nerve cell adhesion molecule) from the small cell bronchial carcinoma cell line SW2 with a molecular weight of 140,000 daltons. These stable transfected cells were prepared as follows. The coding region of the 140000 Dalton isoform of NCAM was cloned from the cDNA by the PCR method (polymerase chain reaction). CDNA was synthesized from poly A + RNA derived from the human small cell bronchial carcinoma cell line SW2. Three overlapping DNA fragments were prepared, then each cloned and sequenced in pSK + Bluescript (Stratagen GMGH, Zürich). Fragment 1 was cut with a restriction enzyme (EcoRI / NotI) to isolate the cut pieces. Fragment 2 was isolated by cutting with EcoRI / BstBI. Fragment 3 was isolated by cutting with BstBI / NotI. The three cleavage fragments were religated to obtain the coding sequence for human 14,000 dalton NCAM. This clone was then subcloned into the eukaryotic expression vector pRC / CMV (Invitrogen, Heidelberg) using the HindIII / NotI restriction enzymes. Mouse Play B Cell Line B-300.19 (Reth, et al, Nature 322 , 840-842, 1986) by electroporation. For this, 40 ng of uncleaved plasmid ⁷ Inserted into individual mouse cells. Geneticin-resistant cells were then selected. The vector used contains a geneticin resistance gene. Resistant clones were examined for NCAM surface expression. Clones with a particularly high degree of homogeneous expression of NCAM were selected. This clone was positive for antibody SEN7 and other known anti-NCAM antibodies. This clone was negative for anti-cluster w4 / CD24 antibody SWAII. [Example 7] Competition between antibody SEN7 and other NCAM antibodies Three different epitopes on small cell bronchial carcinoma (Moolenaar, CECK. Et al, Cancer Res. 50 1102-1106, 1990 and Hida, T .; et al, Br. J. Cancer, 63 , Su ± 1. NCAM antibody recognizing XIV, 24-28, 1991) was investigated for its effect of blocking SEN7 binding to bronchial carcinoma cells. In the radioimmuno experiment, first 10 ^Five Individual cells were treated with an excess of competing primary NCAM antibody. Then the cells ¹²⁵ Incubated with I-labeled antibody SEN7 (using half-saturating concentration). Unbound antibody was washed away to determine bound radioactivity. As shown in Table 1 below, it was found that there was no or negligible competition of SEN7 with other antibodies for binding to tumor cells. Example 8 Tissue Immunoperoxidase Staining Tissue samples of tumor and healthy tissues were examined by immunoperoxidase staining. Frozen sections (5 μm thick) are prepared and fixed on adhesive-coated slides. 0.3% (V / V) H in methanol ₂ O ₂ After pretreatment with porcine serum (2%) and sections are coated with SEN7 solution and incubated for 1 hour at room temperature. The sections are then washed and treated first with peroxidase-conjugated anti-mouse rabbit serum and then with peroxidase-conjugated anti-rabbit pig serum. Peroxidase is visualized with 3,3'-diaminobenzidine as chromogen. Sections are counterstained with hematoxylin. The results are summarized in Table 2 below. Example 9 Xenograft Examination in Mice Preparation : 10 ⁷ The washed cells of the individual cell line SW2 are each subcutaneously injected into female IC Rnu / nu mice (4-6 weeks old) bred under pathogen-free conditions. The examination is started as soon as the tumor has reached a weight of approximately 100 mg (approximately 2-3 weeks after injection). Method : Equal amount of SEN7 antibody (6 μg / animal, using 12 μCi ¹²⁵ I-labeled) and MG-1 antibody (6 μg / animal, 12 μCi as control) ¹³¹ The mixture of I-labeled) is injected intravenously into the animal. The control antibody, like the antibody SEN7, belongs to class Ig G1. Four mice each are killed after 2, 4 and 7 days, various organs are washed with PBS and weighed. The two antibodies are measured using a 2-channel gamma counter (15-80 keV and 260-470 keV). The results are summarized in Table 3 below.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁶ Identification number Office reference number FI C07K 16/18 8318-4H C12N 5/10 15/02 15/09 G01N 33/574 D 8310-2J 33/577 B 8310-2J // A61K 39/00 H 9284-4C (C12P 21/08 C12R 1:91) 9281-4B C12N 15/00 A

Claims (1)

[Claims]   1. A murine monoclonal antibody designated SEN7.   2. Name SEN7.2a. 4 and deposit number DSM ACC2050, A hybridoma cell line secreting the monoclonal antibody of claim 1.   3. Small cell carcinoma of the lung, characterized by being bound by the antibody of claim 1. Antigen from tumor cells.   4. Characterized by being a membrane-bound glycoprotein having a molecular weight of 180,000 The antigen according to claim 3, wherein   5. A hypervariable region derived from the monoclonal antibody according to claim 1, Antibody having a murine hypervariable region, a human framework region and a constant region .   6. An antibody comprising the antibody according to claim 1 or 5 as an antibody component. Body conjugation.   7. For the preparation of a preparation for the treatment and / or diagnosis of small cell carcinoma of the lung Use of the antibody according to claim 1 or 5 or the antibody conjugate according to claim 6.   8. Claims 1 or 5 for the treatment and / or diagnosis of small cell carcinoma of the lung. Use of the antibody described above or the antibody conjugate according to claim 6.