Monoclonal antibodies in oncology (original) (raw)

Reactivity of a monoclonal antibody with tissues and tumors from the human breast. Immunohistochemical localization of a new antigen and clinicopathologic correlations

PubMed, 1984

The reactions of a monoclonal antibody to the MCF7 breast cancer cell line were immunohistochemically studied on a variety of breast tumors, primary and metastatic, on mammary epithelium and on nonneoplastic breast lesions. A high proportion of positive reactions was observed in ductal, lobular, and tubular carcinomas as well as in mammary Paget's disease. Mucinous, medullary, and papillary carcinomas showed a low incidence of reactivity. Carcinomas with metaplasia, carcinoids, and nonepithelial breast tumors were unreactive with the antibody. Positive immunostaining was documented also in nodal and extranodal metastatic lesions. The staining of nodal metastases was correlated with the positive reaction of the primary tumor. Reactivity was widely distributed in normal breast epithelial cells and in benign breast lesions. Staining of nonneoplastic mammary epithelial was associated with reactivity of adjacent neoplastic tissues. Staining differences between nonneoplastic and neoplastic mammary tissues were related to the intensity and cytologic distribution of the labeling. Heterogeneous reactivity of morphologically similar cells was documented in nonneoplastic and neoplastic breast epithelial cells as well as in nodal and extranodal breast carcinoma metastases. Immunohistologically detectable antigen was not correlated with prognostic factors such as histologic grade or nodal status. A retrospective study of T1NO cases failed to substantiate any prognostic value for the reactivity of primary breast tumors with this monoclonal antibody.

Generation of monoclonal antibodies reacting with normal and cancer cells of human breast

Cancer Research

Fusion of the murine myeloma line P3-X63-Ag8-U1 with spleen cells from a mouse immunized with a membrane preparations (CM) of a mucinous ovarian cystoadenocarcinoma yielded two monoclonal antibodies, MOv1 and M0v2, which reacted by solidphase radioimmunoassay with immunizing tumor CM but were unreactive with normal kidney CM as well as with plasma pro teins and peripheral blood cells from the immunizing carcinoma patient.

A monoclonal antibody (B72.3) defines patterns of distribution of a novel tumor-associated antigen in human mammary carcinoma cell populations

International Journal of Cancer, 1982

We report here both the range and patterns of reactivit y of an lgG, monoclonal antibody, 872.3, prepared against human metastatic mammary carcinoma cells. When the avidin-biotin complex (ABC) immunoperoxidase technique was used on tissue sections, monoclonal 672.3 reacted with 19 of 41 (46%) primary mammary carcinomas and I3 of 21 (62 %) metastatic lesions, either in axillary lymph nodes or at distal sites. Variable concentrations of antigen, recognized by 672.3, were obsewed among mammary tumors, as well as among different cell populations of a given tumor mass. Several patterns of antigen distribution were observed: membrane, diffuse cytoplasmic, focal, apical and marginal. No reactivity was observed to normal mammary epithelium, stroma, or lymphocytes of the breast, nor to any cell types in a variety of other normal human tissues, melanomas, and sarcomas. Reactivity with all of four colon carcinomas was also observed. Assay of serial sections of mammary carcinomas with 672.3 and a monoclonal antibody directed against carcinoembryonic antigen demonstrated that these antigens were both distinct and non-coordinately expressed.

A method for distinguishing benign from malignant breast lesions utilizing antibody present in normal human sera

Cancer, 1979

A sensitive immunoperoxidase technique was utilized 1) to detect the presence in normal human serum of antibody directed against breast carcinoma cells (tumor associated antibody-TAA) and 2) to determine whether this antibody could be used to discriminate between benign and malignant breast epithelium in sections of formalin fixed paraffin embedded tissue. A total of 16 benign and 13 malignant breast lesions were examined for evidence of binding of human immunoglobulin, before and after application of normal human AB serum containing the putative tumor associated antibody-TAA. Malignant cells showed significant binding of human immunoglobulin (TAA); benign or normal cells did not. Clear immunohistological separation of benign and malignant breast lesions appears possible by this method.

Detection of Antigens Recognized by a Novel Monoclonal Antibody in Tissue and Serum from Patients with Breast Cancer

Cancer Research, 1986

37'C. Culture fluids were collected, and cells and cell debris were removed by centrifugation at 4000 x g (10 mm at 4C) followed by filtration through 0.45-tim Millipore membrane filters. Fluids were stored at â€"20'C. Portions of 4â€"5 liters of culture fluid were concen trated by means of a Minitan apparatus (Millipore Corp.) to a volume of approximately 100 mL Solid ammonium sulfate was slowly added to bring to 50% saturation, and after standing overnight at 4'C, protein precipitates were collected by centrifugation at 10,000 x g (15 miii at 4C). Precipitates were redissolved in 4â€"5 ml PBS and dialyzed exten sivelyagainstPBS.The final preparationcontained2â€"3 mg protein! ml. Hybridoma Production. BALB/c mice were immunized by an i.p. injection of0.5 mg of the aboveprotein preparation once every 21 days (approximately 20% pure asjudged by SDS-polyacrylamide gel electro phoresis and protein staining) were eluted with 2.5 M MgC12.The antigenpreparationwasimmediatelydiluted 4 times with 0.1 M car bonate buffer, pH 9.6, and aliquots were stored at â€"80T.The protein concentration was determined by the method of Bradford (8) using bovine serum albumin as standard.

Expression of monoclonal-antibody-defined antigens in fractions isolated from human breast carcinomas and patients' serum

Cancer Immunology Immunotherapy, 1995

The aim of this study was to examine tissue from patients with breast carcinoma or benign breast disease for the presence of monoclonal-antibody-defined antigens, including the MUC1 mucin and carcinoembryonic antigen CEA. The tests were performed by sodium dodecyl sulphate/polyacrylamide gel electrophoretic separation of proteins, electrophoretic transfer to nitrocellulose membranes and immunostaining with the monoclonal antibodies. Some of the antigens identified are known to circulate at high levels in some but not necessarily all, breast carcinoma patients. Serum from a panel of ten breast cancer patients was subjected to a fractionation procedure designed to release antigen from immune complexes, and again these samples were analysed for the presence of monoclonal-antibody-defined antigens. A high frequency of positive reactions was detected by the anti-MUC1 monoclonal antibody C595 with both breast carcinoma subcellular membrane fractions as well as antigen fractions eluted from circulating immune complexes. No reactions were observed with equivalent materials from benign breast disease samples. The findings illustrate the variability in antigen expression between breast tumours. The data also indicate that a proportion of patients respond to their tumour by the production of antibodies that recognise the MUC1 antigen in their circulation.

Detection of the tumour-associated antigens recognized by the monoclonal antibodies hmfg-1 and 2 in serum from patients with breast cancer

International Journal of Cancer, 1984

The levels of the human milk fat globule I and 2 antigens have been measured in the sera of patients with advanced breast cancer, using a "sandwich" type radioimmune assay which exploits the carbohydrate nature of the antigenic determinants. In the series studied. 30 YO of sera from advanced breast cancer patients contained elevated levels of the HMFG-I antigen as compared with 6% of sera from healthy control women, whereas 53% of the advanced breast cancer patients showed elevated levels of HMFG-2 antigen compared with 16,6 YO of the controls. By means of the immune blotting technique, the components carrying the antigenic determinants in sera have been identified and compared for size with those molecules expressing the determinants in primary and secondary breast turnours. Both antibodies react with similar molecular weight components of 320kd and 280kd which are present in serum and tumour samples, although lower molecular weight bands of 230kd and 190kd can be seen in some tumours. These components are much smaller than the glycoprotein (>400kd) present in the human milk fat globule, which carries the antigenic determinants recognized by HMFG-I and 2.

Monoclonal Antibodies for Immunohistochemical Diagnosis of Breast Cancer

The Open Biotechnology Journal

Breast cancer is a leading malignant disease in women worldwide, although its pathology is visually localised. Currently, it has been proven that the parameters of molecular genetic biomarkers, including oncoprotein HER2, proliferation markers Ki-67, oestrogen receptors ER, and progesterone receptors PgR, are associated with breast carcinogenesis and are a reflection of the biological aggression of the tumour. The significance of these biomarkers in signalling pathways and genetic mechanisms of carcinogenesis has been described, as well as the relationship between the expression levels of each biomarker and the tumour response to appropriate therapy. The primary antibody that imparts specificity to IHC is based on the monoclonal antibodies (mAbs) as the main immunoreagent that enables reliable identification of breast cancer cells. The most commonly used antibodies to molecular biomarkers for IHC were determined in accordance with indicators of laboratory use and efficiency (pass ra...