Chemistry: molecular biology and microbiology – Spore forming or isolating process
Patent
1992-06-18
1995-07-18
Lacey, David L.
Chemistry: molecular biology and microbiology
Spore forming or isolating process
435 7021, 4351722, 53038815, 5303888, 53038885, 5303897, 530865, C12N 524, C12N 522, C07K 1630, C07K 1628
Patent
active
054340764
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to novel tumor diagnostic and antitumor reagents, including processes for their preparation and use. In particular aspects, the invention concerns establishment of stable human B cell hybridomas capable of producing human monoclonal antibodies reactive with surface epitopes of human gynecological tumors in a specific manner. The invention further provides for such monoclonal antibodies of known association constants. Certain of these antibodies recognize a proteinaceous surface epitope which has been characterized as a glycoprotein. The invention further relates to the use of these antibodies in the diagnosis and treatment of gynecological malignancies.
a. Monoclonal antibodies of gynecological origin.
The detection of gynecological tumors at an early stage is an essential element in the successful control of these cancers. Likewise, early treatment of these tumors can be determinative of the progression of the disease. Numerous studies have explored the use of immunological reagents for both detection and treatment of tumors including carcinomas of gynecological tissues. Generally, development in this area of cancer research has been toward increasingly refined reagents designed to attack or detect species-specific, tumor-specific, cell surface-specific regions of the diseased tissue.
Some of the earlier approaches to develop immunological reagents for the detection of cervical carcinomas involved immunizing mice with human cervical carcinoma cells. These studies demonstrated certain gains by providing monoclonal antibodies with selected specificity for cervical carcinomas (Koprowska, et al., 1986). The practical problems associated with in vivo use of foreign antibodies in humans, however, such as the induction of a human anti-mouse response when using murine monoclonal antibodies, were recognized as possible elements in the reduction of the efficacy in immunotherapy. In a number of clinical trials to date, murine monoclonal antibodies have been used to treat patients possessing solid tumors. Generally, therapeutic efficacy has been transient or absent using this approach (Houghton, et al., 1985; Oldham, et al., 1984; Sears, et al., 1982).
To overcome these problems, workers have focused on production of chimeric (human-mouse) or human-human antibodies. For instance, it was recognized that increased specificity of immunological reagents which are non-immunogenic when injected into primates or humans could be obtained by replacing mouse cell fusions with human-human fusions to produce hybridomas secreting human monoclonal antibodies. In one approach, the fusion of human lymphocytes with mouse myeloma cells was shown to be a useful procedure for human monoclonal antibody production. Hybridomas of such heteromyeloma cell lines with human cells overcomes some of the problems encountered with construction and maintenance of stable human hybrids such as low concentrations of secreted immunoglobulins and lack of suitable methods for large-scale production.
Using the human-human fusion approach, Hagiwara and Sato were able to produce a human immunoglobulin G (IgG) monoclonal antibody which reacted with autologous cervical carcinoma cells and with tumor cell lines of cervical origin. This monoclonal antibody, however, was not specific to cervical carcinoma epitopes since it reacted with other tumor cells as well, including melanomas, prostate carcinomas, colon carcinomas and hepatomas (Hagiwara & Sato, 1983). A similar approach was used by Glassy and co-workers to obtain human-human monoclonal antibodies specific to a wide range of tumor types and tissues of origin including cancer of the vulva. (Glassy, et al., 1987; Glassy and Surh, 1988). Although the studies of Hagiwara & Sato and of Glassy, et al. were successful in obtaining species-specific (human-human) monoclonal antibodies, the cell surface specificity of these antibodies was not extensively characterized.
Tumor immunotherapy is based on the concept that malignant tumor cells express unique cell surface epitopes not found i
REFERENCES:
Freedman et al., Hybridoma, vol. 10, pp. 21-33, 1991.
Klein, J. Interferon Res, vol. 7, #5, pp. 583-589, 1987 (Abstract Thereof).
Freedman et al., Gynecol. Oncol. vol. 29, pp. 337-347, 1988.
Ioannides et al., Anticancer Res, vol. 9, pp. 81-86, 1989.
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Freedman Ralph S.
Ioannides Constantin G.
Patenia Rebecca S.
Tomasovic Barbara J.
Board of Regents , The University of Texas System
Lacey David L.
Schwadron Ron
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