Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1989-09-29
1994-08-16
Scheiner, Toni R.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
436 63, 436 64, 436813, 436512, 436533, 436534, 5303877, 53038815, 5303888, 53038885, 5303897, G01N 33574, G01N 33546, C07K 1514
Patent
active
053386612
DESCRIPTION:
BRIEF SUMMARY
FIELD OF INVENTION
The present invention relates to a tumour-associated antigen, an antibody directed against the antigen, a diagnostic agent comprising the antigen or the antibody, a pharmaceutical composition comprising the antigen or the antibody, and the use of the antigen or the antibody for a variety of diagnostic or therapeutic purposes.
BACKGROUND OF THE INVENTION
The possibility of developing more precise methods of detecting and diagnosing cancer by identifying and characterizing tumour-associated antigens (i.e. antigens expressed by tumours) is of great medical interest.
Monoclonal antibodies against tumour-associated antigens may play an important role for the detection of cancer because of their greater specificity. To date most of the monoclonal antibodies raised against cancer-associated antigens have been of mouse origin, being expressed by hybridomas resulting from a fusion of spleen cells from a mouse immunized with a human cancer cell line or cells from a cancer patient with a mouse myeloma cell line. Immunogenicity in the mouse is a requirement for antigens recognized by murine monoclonal antibodies and they do not necessarily correspond to antigens recognized by human antibodies. In addition, the therapeutic value of these murine monoclonal antibodies may be limited since patients recognize these antibodies as foreign proteins and may therefore develop an adverse immune response against the murine antibody. The result may be a neutralization of the therapeutic effect and triggering of potentially dangerous allergic reactions.
Human hybridoma antibodies may be more promising as diagnostic and therapeutic agents for administration to patients with cancer under the assumption that human monoclonal antibodies are less immunogenic in humans than heterologous antibodies and are capable of recognizing the relevant antigens.
Problems related to the specificity of murine monoclonal anti-tumour antibodies are illustrated by the colon adenocarcinoma antibody 17-A1, which has been used in diagnosis and therapy, but has now been found to react with normal as well as tumour tissue (Hybridoma 5 Suppl. 1, 1986, special issue on Ca-17-A1, ed. Z. Steplewski).
The immune response in patients against administered murine monoclonal antibody has been described by numerous investigators (e.g. H. F. Sears et al., Lancet 1985, i:762-765; and M. S. Mitchell et al., Prog. Cancer Res. Ther. 21, 1982, Raven Press, New York).
Colo-rectal cancer is one of the most frequently occurring cancers and one of the major causes of death from cancer. The prognosis of this cancer type has not improved for a long period of time, and novel methods for the detection of colo-rectal cancer and adjuvant therapy concomitantly with surgery thereof are therefore needed.
Therefore, a need exists for a human carcinoma tumour-associated antigen, in particular one which is substantially not expressed by normal tissue, and antibodies against such an antigen for diagnostic and therapeutic purposes.
DESCRIPTION OF THE INVENTION
Accordingly, the present invention relates to a human carcinoma-associated antigen which has an apparent molecular weight of about 43,000 and an isoelectric point in the range of about 5.4-6.2, and which has at least one epitope which is reactive with a monoclonal antibody produced by the human hybridoma cell line B9165 (ECACC 87040201), or an analogue thereof.
The term "analogue" is used in the present context to indicate a protein or polypeptide of a similar amino acid composition or sequence as the present antigen, allowing for minor variations which do not have an adverse effect on the immunogenicity of the analogue. The analogous polypeptide or protein may be derived from another source than carcinoma tissue such as from a recombinant organism or may be partially or completely of synthetic origin. The term is further intended to mean any derivative of The antigen such as an immunogenic subsequence thereof.
Immunocytochemical analysis by standard procedures using a monoclonal antibody with specific reactivi
REFERENCES:
Girardet, et al.; J. of Immunology; 136(4):1497-1503 (1986); Immunochemical Characterization of Two Antigens Recognized by New Monoclonal Antibodies Against Human Colon Carcinoma.
Herlyn, et al.; PNAS; 76(3):1438-1442 (1979); Colorectal Carcinoma-Specific Antigen: Detection by Means of Monoclonal Antibodies.
Herlyn, et al.; Cancer; 27:769-774 (1981); Monoclonal Anticolon Carcinoma Antibodies in Complement-Dependent Cytotoxicity.
Brown, et al.; Bioscience Reports; 3:163-170 (1983); A Monoclonal Antibody Against Human Colonic Adenoma Recognizes Difucosylated Type-2-Blood-Group Chains.
Thompson, et al.; Cancer; 47:595-605 (1983); Monoclonal Antibodies to Human Colon and Colorectal Carcinoma.
Kaszubowski, et al.; Cancer Res.; 44:1194-1199 (1984); A Cytotoxic Monoclonal Antibody to Colon Adenocarcinoma.
Morgan, et al.; Hybridoma; 3(3):233-245 (1984); Monoclonal Antibodies to Human Colorectal Tumor-Associated Antigens: Improved Elicitation and Subclass Restriction.
Drewinko, et al.; Cancer Res.; 46:5137-5143 (1986); New Monoclonal Antibodies against Colon Cancer-Associated Antigens.
Gazdar, et al.; Cancer Res.; 41:2773-2777 (1981); Levels of Creatine Kinase and Its BB Isoenzyme in Lung Cancer Specimens and Cultures.
Syamal Raychaudhuri, Yukihiko Saeki, Hiroshi Fuji and Heinz Kohler "Tumor-Specific Idiotype Vaccines", vol. 137, pp. 1743-1749, No. 5 "The Journal of Immunology".
Alfred Nisonoff, John E. Hopper and Susan B. Spring, "The Antibody Molecule".
Ronald C. Kennedy, Joseph I. Mednick and Gordon R. Dreesman, "Anti-Iodiotypes and Immunity".
Borup-Christensen Per
Erb Karin
Jensenius Jens C.
Cooper Iver P.
Scheiner Toni R.
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