Circulating breast epithelial antigens (CBEAgs) released into the blood stream detect tumors and inform on the Ag make-up of the tumor. We developed sensitive and specific techniques for CBEAgs identification and extraction from serum. Our monoclonal antibodies (MoAbs) identify several CBEAgs and determine their serum levels, study their metabolism and their participation in immunocomplexes. Thus, we continue to create MoAbs against CBEAgs and use them in diagnostic and in host immunoresponse studies and at the morphological level to determine how they are released. With these approaches, we plan to: a) continue isolating and characterizing these CBEAgs. Using different isolation procedures, conditioned by the source of the Ags (free or in immunocomplex form) their Ag heterogeneity and degradation will be examined; b) study the fate of CBEAgs in the circulation (their physicochemical state, catabolic destruction, etc.); c) investigate how these CBEAgs are released and enter the circulation at the EM level; d) investigate the clinical significance of these CBEAgs, their associated antibodies and circulating immunocomplexes (CIC), and their ability to monitor benign and malignant lesions of the breast. Concurrently, we will investigate how isolated CBEAgs and their corresponding MoAbs may affect immunoreactants of breast cancer patients of varying tumor burden; e) determine the impact of these CBEAgs on the hosts' cellular immune response. Our ability to identify CBEAgs enables us to characterize a tumor mass by its Ag make-up from just a serum sample, determination that could be of therapeutic and/or prognostic value. In addition, knowledge of integrity and physicochemical status of these CBEAgs in circulation and how they are disposed of could help assess the patient's immune status. The ultrastructural study of the release of these CBEAgs could provide us with understanding about the way in which the tumor interacts with the host at the cellular level, while experimentation that we also propose will focus on the influence of these CBEAgs on the cellular immunity of the breast cancer patient.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA039932-05
Application #
3179326
Study Section
Chemical Pathology Study Section (CPA)
Project Start
1984-09-16
Project End
1990-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
5
Fiscal Year
1988
Total Cost
Indirect Cost
Name
John Muir Memorial Hosp (Walnut Crk, CA)
Department
Type
DUNS #
City
Walnut Creek
State
CA
Country
United States
Zip Code
94598
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Peterson, J A; Couto, J R; Taylor, M R et al. (1995) Selection of tumor-specific epitopes on target antigens for radioimmunotherapy of breast cancer. Cancer Res 55:5847s-5851s
Ceriani, R L; Blank, E W; Couto, J R et al. (1995) Biological activity of two humanized antibodies against two different breast cancer antigens and comparison to their original murine forms. Cancer Res 55:5852s-5856s
Ortel, T L; Quinn-Allen, M A; Keller, F G et al. (1994) Localization of functionally important epitopes within the second C-type domain of coagulation factor V using recombinant chimeras. J Biol Chem 269:15898-905
Peterson, J A; Ceriani, R L (1994) Breast mucin and associated antigens in diagnosis and therapy. Adv Exp Med Biol 353:1-8

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