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      In vitro Anti‐tumor Activity of Anti‐c‐ erbB‐2 × Anti‐CD3ɛ Bifunctional Monoclonal Antibody

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          Abstract

          With the aim of developing an effective cancer immunotherapy for common epithelial cancer, a new class of bifunctional antibody (BFA) was developed; one arm of this BFA recognized c‐ erbB‐2 gene product, and the other arm recognized CD3ɛ, a T‐cell specific surface antigen. Application of this BFA with human peripheral blood lymphocytes exhibited specific anti‐tumor activity in vitro on a breast tumor cell line, ZR‐75–1, which expressed abundant c‐ erbB‐2 gene product on its cell surface. These results indicate that BFA recognizing an oncogene product on cell surface is a potential new agent for cancer immunotherapy.

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          Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor.

          T. Yamamoto, S Ikawa, T. Akiyama … (2015)
          A novel v-erb-B-related gene, c-erb-B-2, which has been identified in the human genome, maps to human chromosome 17 at q21 (ref. 40), and seems to encode a polypeptide with a kinase domain that is highly homologous with, but distinct from, that of the epidermal growth factor (EGF) receptor. The c-erb-B-2 gene is conserved in vertebrates and it has been suggested that the neu gene, detected in a series of rat neuro/glioblastomas, is, in fact, the rat c-erb-B-2 gene. Amplification of the c-erb-B-2 gene in a salivary adenocarcinoma and a gastric cancer cell line MKN-7 suggests that its over-expression is sometimes involved in the neoplastic process. To determine the nature of the c-erb-B-2 protein, we have now molecularly cloned complementary DNA for c-erb-B-2 messenger RNA prepared from MKN-7 cells. Its sequence shows that the c-erb-B-2 gene encodes a possible receptor protein and allows an analysis of the similarity of the protein to the EGF receptor and the neu product. As a consequence of chromosomal aberration in MKN-7 cells, a 4.6-kilobase (kb) normal transcript and a truncated 2.3-kb transcript of c-erb-B-2 are synthesized at elevated levels. The latter transcript presumably encodes only the extracellular domain of the putative receptor.
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            Preparation of bispecific antibodies by chemical recombination of monoclonal immunoglobulin G1 fragments.

            M. Brennan, P Davison, H Paulus (1985)
            Preparation of bispecific antibodies by the chemical reassociation of monovalent fragments derived from monoclonal mouse immunoglobulin G1 is inefficient because of side reactions during reoxidation of the multiple disulfide bonds linking the heavy chains. These side reactions can be avoided by using specific dithiol complexing agents such as arsenite and effecting disulfide formation with a thiol activating agent such as 5,5'-dithiobis(2-nitrobenzoic acid). In this way bispecific antibodies were obtained in high yield and free of monospecific contaminants from monoclonal mouse immunoglobulin G1 fragments. The bispecific antibodies were used as agents for the selective immobilization of enzymes.
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              Overexpression of the EGF receptor-related proto-oncogene erbB-2 in human mammary tumor cell lines by different molecular mechanisms.

              S Amsbaugh, N Popescu, Johann Kraus … (1987)
              Amplification of the erbB/EGF receptor and a structurally related gene, designated erbB-2, have previously been detected in a variety of human tumors. In a series of human mammary tumor cell lines, analysis of transcripts of these genes revealed elevated levels of one or the other in more than 60% of tumors analyzed. Eight cell lines demonstrated erbB-2 mRNA levels ranging from 4- to 128-fold above those of normal controls. erbB-2 expression was evaluated in comparison to the expression level of actin observed in these cell lines. There was no evidence of an aberrantly sized erbB-2 transcript in any of these lines. Immunoblot analysis indicated elevation in levels of the 185-kd product of the erbB-2 gene expressed by these cells. In four lines erbB-2 gene amplification in the absence of an apparent gene rearrangement was demonstrated. In a representative cell line of this type, SK-BR-3, the amplified erbB-2 gene copies were located in an aberrant chromosomal location. Four additional cell lines, which demonstrated 4- to 8-fold overexpression of erbB-2 mRNA, did not exhibit gene amplification. In a representative cell line of this type ZR-75-1, an apparently normal chromosomal location was found for the erbB-2 gene. Our findings indicate that overexpression of the erbB-2 gene in mammary tumor cell lines is frequent and associated with different genetic abnormalities.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Jpn J Cancer Res
                Journal ID (iso-abbrev): Jpn. J. Cancer Res
                Journal ID (doi): 10.1111/(ISSN)1349-7006a
                Journal ID (publisher-id): CAS
                Title: Japanese Journal of Cancer Research : Gann
                Publisher: Blackwell Publishing Ltd (Oxford, UK )
                ISSN (Print): 0910-5050
                ISSN (Electronic): 1876-4673
                Publication date (Print): June 1992
                Volume: 83
                Issue: 6 ( doiID: 10.1111/cas.1992.83.issue-6 )
                Pages: 563-567
                Affiliations
                [ 1 ]Viral Diseases Research Division, Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd., 463‐10 Kagasuno, Kawaucki‐cho, Tokushima 771‐01
                [ 2 ]Cell Engineering Division, Bioscience Laboratory, Earth Chemical Co., Ltd., 1122‐73 Kitamachi, Nishihama, Ako‐shi, Hyogo 678‐02
                [ 3 ]Department of Molecular Biology, Nagoya City University School of Medicine, Mizuhocho, Mizuho‐ku, Nagoya 467
                [ 4 ]Growth Factor Division, National Cancer Center Research Institute, Tsukiji 5‐1‐1, Chuo‐ku, Tokyo 104
                Author notes
                [*] [* ] 5To whom requests for reprints should be addressed.
                Article
                Publisher ID: CAE563
                DOI: 10.1111/j.1349-7006.1992.tb00126.x
                PMC ID: 5918874
                PubMed ID: 1353752
                SO-VID: fb12e7f5-3bad-4ab3-aa5c-2885214802c5
                History
                Page count
                References: 25, Pages: 5
                Categories
                Subject: Rapid Communication
                Custom metadata
                source-schema-version-number 2.0
                cover-date June 1992
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_NLMPMC version:4.6.9 mode:remove_FC converted:04.11.2015

                Keywords: key words,monoclonal antibody,anti‐c‐erbb‐2,anti‐cd3ɛ,bifunctional antibody,cancer immunotherapy
                Data availability:
                Keywords: key words, monoclonal antibody, anti‐c‐erbb‐2, anti‐cd3ɛ, bifunctional antibody, cancer immunotherapy

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