Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,... – Anti-idiotypic
Patent
1996-02-26
1999-01-12
Feisee, Lila
Drug, bio-affecting and body treating compositions
Immunoglobulin, antiserum, antibody, or antibody fragment,...
Anti-idiotypic
5303881, 53038825, 435 696, 435327, 435337, 435346, 4241411, A61K 39395, C07K 1600, C12N 1686, C12N 1500
Patent
active
058583610
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to monoclonal anti-idiotypic antibodies reacting with anti-CA125 antibodies and competing with CA125 in binding to said anti-CA125 antibodies.
Furthermore, the invention relates to hybridomas producing said monoclonal anti-idiotypic antibodies. The present invention also relates to a method for the production of said monoclonal anti-CA125 antibodies and to pharmaceutical compositions containing them. These pharmaceutical compositions are useful for the treatment of CA125-positive malignant tumors, particularly epithelial ovarial cancer.
Up to now, the positive effect of an immunotherapy using tumor-associated antigens or tumor cells of ovarian carcinomas is still unproved. Although many unique tumor-associated antigens have been described and were used for vaccinations, a tumor rejection could only be seen occasionally and the failure of the immune system to destroy tumor cells is not clearly understood; Raychaudhuri et al., J. Immunology 139 (1987), 271. One of the reasons might be that different classes of available tumor-associated antigens (TAA) fail to induce an effective anti-tumor response; Dalgleish and Kennedy, Vaccine 6 (1988), 215, and Lee et al., Proc. Natl. Acad. Sci. USA 82 (1985), 6286. The most common TAAs belong to the class III tumor-associated antigens and are found on both malignant and a number of normal cells, but they are usually expressed at a higher concentration on the malignant cells.
Therefore, an explanation for the absence of an anti-tumor immunity in patients might be the close relationship of the tumor-associated antigens (class III) and self-antigens and that the host's immune system has been tolerized by the tumor antigen by slowly increasing antigen doses. Furthermore, a patient suffering from a carcinoma is mostly immunosuppressed; Wagner et al., Tumordiagnostik & Therapie 11 (1990), 1.
An effective way to overcome an experimentally induced tolerance is to present the relevant antigen in a different molecular environment to the tolerized immune system, but this can only be done for well-defined and easily purifyable antigens: Raychaudhuri et al., J. Immunology 137 (1986), 1743. According to the network hypothesis of Niels Jerne, the immune system consists of antibodies and lymphocytes which interact through complementary structures; Jerne, Ann. Immunol. (Paris) 125C (1974), 373. The interlymphocytic connections depend on the variable region structures presented on antibody molecules or specific receptors. In this system, "internal image" antibodies express a special idiotype mimicking the original antigenic epitope, which can thus be presented to the immune system by the variable region of such antibody molecules. Such antibodies are defined as anti-idiotypic antibodies-beta (=Ab2.beta.), if they bear the internal image of a distinct antigen; Cerny and Hiernaux, "Concept of Idiotypic Network: Description and Functions in Idiotypic Network and Diseases", Cerny and Hiernaux, Eds., American Society for Microbiology, Washington, 1990; Raychaudhuri et al., J. Immunology, 139 (1987), 271.
The alternative approach to overcome immunological tolerance is to initiate the idiotypic network using antibodies (named Ab1) against a tumor-associated antigen. This induces the production of anti-idiotypic antibodies (Ab2.beta.) mimicking the "internal image" of the tumor-associated antigen. The principle is to transform the critical epitope of the TAA into an idiotypic determinant expressing the mirror image of the tumor-associated antigen on the surface of the antigen binding region of an antibody; Cerny and Hiernaux, supra. The Ab1 may induce Ab2, which are then capable of inducing Id.sup.+ (Ab1.sup.+) B-cells or Id.sup.+ T.sub.H cells or cause a suppression of the proposed anti-tumor reaction by the induction of Id.sup.+ T.sub.S cells; Cerny and Hiernaux, supra, Raychaudhuri et al., J. Immunology, 137 (1987), 2096, Wettendorff et al., Proc. Natl. Acad. Sci. USA 86 (1989), 3787.
In summary, the Ab2.beta. is able to induce a specific anti-tumor immunity in t
REFERENCES:
Ransberg et al, Clin. Chem. 36/1, 164-167 (1990) Evidence for Interaction of Human Anti Id Antibodies with CA125 Determination in a Patent after Radioimmunodetection.
Ray Chaudline et al J Immunol 139:271-278, 1987 (Jul. 1).
Morrison Science vol. 229, pp. 1202-1206 (1985).
Sandhu, Critical Reviews in Biotechnology vol. 12/5,6 1992 pp. 440-443.
Schlebusch Harald
Wagner Uwe
Bansal Geetha P.
Feisee Lila
White John P.
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