Immunohistochemical localization and molecular characteristics of three monoclonal antibody‐defined epitopes detectable on carcinoembryonic antigen (CEA)

Abstract

Three murine monoclonal antibodies (MAbs) reactive to different epitopes on CEA were selected according to their ability to bind to various human tissue sections. The most selective MAb, BW 431/31, bound to the majority of colon carcinomas but only faintly to normal colon mucosa. In addition to the tissues stained by MAb BW 431/31, MAb BW 250/183 reacted with granulocytes, colon mucosa and faintly with pancreatic ducts. The third MAb, BW 374/14, reacted with granulocytes, colon mucosa, strongly with pancreatic ducts and with alveolar and bronchial epithelium. The antigenic determinants recognized by the 3 MAbs in human tissue sections were resistant to formaldehyde fixation and paraffin embedding as well as to periodic acid oxidation and neuraminidase treatment. The last two treatments suggest that the epitopes are protein in nature. Using MAb affinity chromatography, 3 antigen preparations were isolated from a human colon carcinoma xenograft with an approximate molecular weight of 180 kd. These preparations were shown to bear the epitopes from each of the MAbs and from a polyclonal antiserum specific for purified CEA. Furthermore, the ability of MAb BW 431/31 to localize its antigenic determinant in vivo on a human colon carcinoma xenograft is evaluated and its possible application in the patient is suggested.

A chimeric receptor that selectively targets membrane-bound carcinoembryonic antigen (mCEA) in the presence of soluble CEA

“…The reactivity of humBW431/26 is restricted to malignant and premalignant tissues whereas no reactivity with normal tissues was found apart from a low intrinsic reactivity with the luminal part of the colon mucosa. [10][11][12][13] To obtain a chimeric T cell receptor we fused the DNA coding for the anti-CEA single chain antibody fragment (scFv) in frame to the CH2/CH3 domains of the human IgG1 14 and the transmembrane and intracellular domain of the ␥-signalling chain derived from the Fc⑀RI␥-receptor. 2 The DNA coding for the chimeric receptor is expressed under control of the RSV LTR after transfection into the murine T cell line MD45.…”

Radioimmunoimaging of Non-Small Cell Lung Cancer with111In- and99MTc-Labeled Monoclonal Anti-Cea-Antibodies

“…Most non-small cell lung cancers react with CEA immunohistochemically (38,(41)(42)(43)(44)(45)(46)(47)(48). With this antibody, intense immunohistochemical staining is obtained both in squamous cell and adenomatous cancer cells (Fig.…”

“…The monoclonal antibody BW 431/31, also provide by Behringwerke AG, is a F(ab'), fragment of an antibody produced against CEA (38). The fragments, to which DTPA-moieties were attached, were labeled with "'In (InCI,, Amersham, England).…”

The Antibody Approach of Labeling Blood Cells

“…A similar antibody, reported first by Bosslet et al (Bosslet, 1985) was later developed and produced as MAb BW-250/183 by Behringwerke AG, Germany (Table 1). It recognizes the same NCA-95 antigen on granulocytes and its in-vivo properties are very similar to MAb AK-47.…”

“…These developments offer the promise to selectively label specific cell types in blood, in vitro or in vivo, thus overcoming the need for complex and damaging cell separation steps. Monoclonal antibodies directed against specific cellular antigens continue to be identified and developed (Buchegger, 1984;Bosslet, 1985;Coller, 1985;Thakur, 1987Thakur, , 1988McAfee, 1988a). A number of these have attracted considerable interest and are presently undergoing active investigation.…”