Dose dependent localisation of a monoclonal F(ab')2 fragment against CEA in the mouse xenograft model.
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Biomedical subjects
Publications and source records attributed to G A Rawlins.
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A mouse monoclonal antibody, W14A, has been prepared which reacts with intact human chorionic gonadotropin and its beta-subunit, showing less than 2% cross-reactivity towards the alpha-subunit and 0.5% cross-reactivity towards the beta-subunit of luteinizing hormone. The reagent is suitable for the radioimmunolocalization of choriocarcinoma and trophoblastic teratoma in humans. A preliminary radioimmunoassay has been developed.
A new monoclonal antibody, that binds to CEA and with low cross-reactivity with NCA, has been raised to an antigen expressed on HT29 colon tumour cells. This antibody (H58) reacts strongly with high-molecular-weight protein (50 X 10(4)) isolated from a crude plasma membrane preparation of HT29 cells as well as binding to purified CEA of molecular size (20 X 10(4)) isolated both from those cells and liver metastases of colon tumour. H58 binds to an epitope sterically unrelated to the binding site of the previously described anti-CEA monoclonal antibody MA/1 and our routine anti-CEA polyclonal serum PKIG. Augmented binding of antibody to either the cell membrane preparation or conventional CEA can be achieved using a mixture comprising equal weights of specific immunoglobulin from H58 and MA/1. The value of solid-phase binding assays using microtitre plates for selecting potentially useful antibodies is discussed.
Binding characteristics of two mouse monoclonal antibodies MA/1 and MA/200 raised to carcinoembryonic antigen (CEA) are presented. Double antibody radioimmunoassay and a solid phase assay confirmed that MA/1 binds weakly to CEA extracted from tumour tissue but strongly to CEA in patients' serum. Antibody MA/200 binds with high affinity to both 'tumour' and 'serum' CEA. Ligand-receptor relationship for MA/1 and MA/200 binding to both tumour CEA and CEA isolated from serum are presented from equilibrium binding data analysed by the method of Scatchard. Co-titration experiments also indicated that MA/1 and MA/200 and an established polyclonal anti-CEA bind to a similar subpopulation of CEA or CEA-like molecules, but the binding data demonstrate that their respective binding sites are chemically different.
Monoclonal antibodies to carcinoembryonic antigen (CEA) promise improved specificity for the measurement of this widely expressed human cancer antigen. A mouse monoclonal antibody binds weakly to CEA in perchloric acid extracts of tumour but strongly to CEA similarly isolated from serum, and its spectrum of cancer detection differs from conventional antisera.
Double-antibody radioimmunoassay using a mouse monoclonal anti-CEA (MA/1) has been used to measure CEA in human serum. Low levels of MA/1-binding CEA have been found in serum from normal individuals and moderately raised levels are sometimes associated with certain non-malignant diseases. As with conventional anti-CEA, the MA/1 antibodies can recognize significant amounts of CEA in serum from patients with a variety of solid tumours. However they appear to recognize a different immunodeterminant and possibly a different population of CEA molecules to, or a subset of, those measured by two routine assays. Studies in which the MA/1 assay was directly compared with the results of the Charing Cross routine and Abbott EIA assays have indicated that different immunological forms of CEA may be expressed in the course of tumour progression but no prognostic value was evident in this study. Our results stress the need to resolve immunological specificities expressed by CEA-like molecules and evaluate their clinical importance.
Positive responses to human chroionic gonadotrophin (H.C.G.) were observed in the macrophage electrophoretic mobility test when lymphocytes from 34/44 patients with various types of cancer and from 7/21 patients with non-malignant disease were tested. Lymphocytes from some pregnant women also responded but those from parous women who were not pregnant did not respond. Positive responses were also obtained with H.C.G. sub-units but not with luteinising hormone.
Lymphocytes from a total of 161 subjects, including normal controls and patients with malignant and non-malignant conditions, have been investigated for their response to myelin basic protein, using the macrophage electrophoretic mobility (MEM) test. It has been confirmed that there was a high level of association between clinically evident cancer and a positive response. Lymphocytes from 24/25 patients with non-malignant inflammatory and ischaemic diseases also gave positive responses. In 46 patients with breast lumps studied before mastectomy or biopsy, the test was positive in 15/19 cases which proved to be malignant and in 5/27 which proved benign on histological examination. In its present form the test is not sufficiently reliable for the diagnosis of early cancer. Our results suggest that tissue necrosis in malignant and non-malignant conditions may be one of the factors resulting in sensitization to antigenic determinants present in preparations of myelin basic protein. Despite its technical difficulties, the test may provide a means of examing some aspects of immune recall not readily revealed by other test systems.
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