Immunohistochemical detection of c-erbB-2 expression by neoplastic human tissue using monospecific and bispecific monoclonal antibodies.
Selected murine monoclonal antibodies (MAb) have been shown to inhibit relevant tumor growth in vitro and in animal models. Recently, bispecific antibodies (BsMAb) have been developed which target cytolytic effector cells via one antibody binding site and tumor antigen by the other specificity. For example, the BsMAb 2B1 possesses specificity for c-erbB-2 and Fc gamma RIII, the low affinity Fc gamma receptor expressed by polymorphonuclear leukocytes (PMN), macrophages and large granular lymphocytes (LGL). The human homologue of the rat neu oncogene, c-erbB-2, has been demonstrated to be amplified in breast, gastrointestinal, lung and ovarian carcinomas. Tumor expression of c-erbB-2 has been shown to be an important prognostic indicator in breast and ovarian carcinomas. The restricted expression of the c-erbB-2 protooncogene product in normal human tissues and the wide distribution of c-erbB-2 expression in such tumors may justify attempts to use an appropriately constructed BsMAb in clinical trials. In this report we have addressed this issue by immunohistochemically evaluating the expression of c-erbB-2 oncogene product in a variety of malignant tumors utilizing 2B1 and the anti-c-erbB-2 monovalent parent of 2B1, 520C9. Among the studied neoplasms, c-erbB-2 expression was detected in 49% of primary carcinomas stained with 520C9 and in 39% of those stained with 2B1. In the group of metastatic tumors, c-erbB-2 oncoprotein was detected in 52% of cases by 520C9 and in 41% by 2B1.(ABSTRACT TRUNCATED AT 250 WORDS)
Garcia de Palazzo
I
I
Fox Chase Cancer Center, Philadelphia, PA 19111.
Klein-Szanto
A
A
Weiner
L M
LM
D000818:Animals; D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000276:immunology* / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism; D066246:ErbB Receptors / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000276:immunology* / Q000378:metabolism*; D011519:Proto-Oncogenes; D018719:Erb-b2 Receptor Tyrosine Kinases
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases