Selective killing of carcinoembryonic-antigen (CEA)-producing cells in vitro by the immunoconjugate cytorhodin-S and CEA-reactive cytorhodin-S antibody CA208
Identifieur interne : 003155 ( Main/Exploration ); précédent : 003154; suivant : 003156Selective killing of carcinoembryonic-antigen (CEA)-producing cells in vitro by the immunoconjugate cytorhodin-S and CEA-reactive cytorhodin-S antibody CA208
Auteurs : Toshiro Iwahashi [Japon] ; Yukiko Tone [Japon] ; Junko Usui [Japon] ; Hiroshi Watanabe [Japon] ; Isamu Sugawara [Japon] ; Sigeo Mori [Japon] ; Hiroshi Okazaki [Japon]Source :
- Cancer Immunology, Immunotherapy [ 0340-7004 ] ; 1989-07-01.
English descriptors
- Teeft :
- Anthracycline, Antibody activity, Antibody conjugates, Antitumor activity, Assay, Behring diagnostics, Behring inst mitt, Carcinoembryonic antigen, Cell line, Cell lines, Cell pellets, Cell pellets fraction, Cell surface, Chloroquine, Citrate buffer, Colo, Conjugate, Conjugation, Cytostatic, Cytostatic assay, Cytostatic effect, Different groups, Drug activity, Endocytotic vesicles, Equivalent dose, Good partner, Growth medium, Hoechst japan, Human colon carcinoma, Immunoconjugate, Immunoconjugates, Immunological activity, Immunosorbent assay, Inhibition assay, Irnmunol methods, Liquid scintillation counter, Lowry method, Lysosomal enzymes, Lysosomotropic agent, Lysosornotropic conjugate, Microtiter plate, Microtiter plates, Monoclonal, Monoclonal antibodies, Monoclonal antibody, Morphological evidence, Negative control, Nude mice, Nude rnice, Other hand, Pharma research laboratories, Pharmacological activity, Positive staining, Proc natl acad, Proliferation assay, Reaction mixture, Rnonoclonal antibodies, Room temperature, Specific interaction, Supernatant fraction, Survival period, Survival time days, Target cells, Test samples, Therapeutic efficacy, Thin sections, Tumor cells, Unbound materials, Unconjugated, Vector labs, Vivo animal experiments, Weil.
Abstract
Summary: Cytorhodin-S, an anthracycline derivative, was covalently coupled to a monoclonal antibody (mAb) CA208, against carcinoembryonic antigen (CEA) in order to achieve selective killing of a CEA-producing colon carcinoma cell line, COLO 205. The conjugate (15 molecules of drugs/antibody) retained substantial antibody activity as well as drug activity as assessed by enzyme-linked immunosorbent assay and 24-h L1210 proliferation assay, respectively. Furthermore, the conjugate inhibited the growth of COLO 205 cells in a short-term cytostatic assay. This cytostatic effect of the immunoconjugate on COLO 205 cells was inhibited in a dose-dependent manner by pretreatment of the cells with unconjugated CA208 mAb. In addition, chloroquine, a lysosomotropic agent, inhibited the cytostatic effect of the immunoconjugate, indicating the involvement of lysosomal enzymes in releasing drugs from the immunoconjugate. The antibody (CA208) was significantly incorporated into the cytoplasm of COLO 205 cells as demonstrated by immuno-electron microscopy. These in vitro results indicate that cytorhodin-S may be a good partner in immunoconjugates. However, in vivo animal experiments with the immunoconjugate revealed that the immunoconjugate was not so effective in prolonging survival. Thus, in vivo efficacy of this immunoconjugate remains to be further improved in application to cancer immunotherapy.
Url:
DOI: 10.1007/BF01665011
Affiliations:
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unit="volume">30</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="239">239</biblScope><biblScope unit="page" to="246">246</biblScope></imprint><idno type="ISSN">0340-7004</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0340-7004</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Anthracycline</term><term>Antibody activity</term><term>Antibody conjugates</term><term>Antitumor activity</term><term>Assay</term><term>Behring diagnostics</term><term>Behring inst mitt</term><term>Carcinoembryonic antigen</term><term>Cell line</term><term>Cell lines</term><term>Cell pellets</term><term>Cell pellets fraction</term><term>Cell surface</term><term>Chloroquine</term><term>Citrate buffer</term><term>Colo</term><term>Conjugate</term><term>Conjugation</term><term>Cytostatic</term><term>Cytostatic assay</term><term>Cytostatic effect</term><term>Different groups</term><term>Drug activity</term><term>Endocytotic vesicles</term><term>Equivalent dose</term><term>Good partner</term><term>Growth medium</term><term>Hoechst japan</term><term>Human colon carcinoma</term><term>Immunoconjugate</term><term>Immunoconjugates</term><term>Immunological activity</term><term>Immunosorbent assay</term><term>Inhibition assay</term><term>Irnmunol methods</term><term>Liquid scintillation counter</term><term>Lowry method</term><term>Lysosomal enzymes</term><term>Lysosomotropic agent</term><term>Lysosornotropic conjugate</term><term>Microtiter plate</term><term>Microtiter plates</term><term>Monoclonal</term><term>Monoclonal antibodies</term><term>Monoclonal antibody</term><term>Morphological evidence</term><term>Negative control</term><term>Nude mice</term><term>Nude rnice</term><term>Other hand</term><term>Pharma research laboratories</term><term>Pharmacological activity</term><term>Positive staining</term><term>Proc natl acad</term><term>Proliferation assay</term><term>Reaction mixture</term><term>Rnonoclonal antibodies</term><term>Room temperature</term><term>Specific interaction</term><term>Supernatant fraction</term><term>Survival period</term><term>Survival time days</term><term>Target cells</term><term>Test samples</term><term>Therapeutic efficacy</term><term>Thin sections</term><term>Tumor cells</term><term>Unbound materials</term><term>Unconjugated</term><term>Vector labs</term><term>Vivo animal experiments</term><term>Weil</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Summary: Cytorhodin-S, an anthracycline derivative, was covalently coupled to a monoclonal antibody (mAb) CA208, against carcinoembryonic antigen (CEA) in order to achieve selective killing of a CEA-producing colon carcinoma cell line, COLO 205. The conjugate (15 molecules of drugs/antibody) retained substantial antibody activity as well as drug activity as assessed by enzyme-linked immunosorbent assay and 24-h L1210 proliferation assay, respectively. Furthermore, the conjugate inhibited the growth of COLO 205 cells in a short-term cytostatic assay. This cytostatic effect of the immunoconjugate on COLO 205 cells was inhibited in a dose-dependent manner by pretreatment of the cells with unconjugated CA208 mAb. In addition, chloroquine, a lysosomotropic agent, inhibited the cytostatic effect of the immunoconjugate, indicating the involvement of lysosomal enzymes in releasing drugs from the immunoconjugate. The antibody (CA208) was significantly incorporated into the cytoplasm of COLO 205 cells as demonstrated by immuno-electron microscopy. These in vitro results indicate that cytorhodin-S may be a good partner in immunoconjugates. However, in vivo animal experiments with the immunoconjugate revealed that the immunoconjugate was not so effective in prolonging survival. Thus, in vivo efficacy of this immunoconjugate remains to be further improved in application to cancer immunotherapy.</div></front></TEI><affiliations><list><country><li>Japon</li></country><region><li>Région de Kantō</li></region><settlement><li>Tokyo</li></settlement><orgName><li>Université de Tokyo</li></orgName></list><tree><country name="Japon"><noRegion><name sortKey="Iwahashi, Toshiro" sort="Iwahashi, Toshiro" uniqKey="Iwahashi T" first="Toshiro" last="Iwahashi">Toshiro Iwahashi</name></noRegion><name sortKey="Mori, Sigeo" sort="Mori, Sigeo" uniqKey="Mori S" first="Sigeo" last="Mori">Sigeo Mori</name><name sortKey="Okazaki, Hiroshi" sort="Okazaki, Hiroshi" uniqKey="Okazaki H" first="Hiroshi" last="Okazaki">Hiroshi Okazaki</name><name sortKey="Sugawara, Isamu" sort="Sugawara, Isamu" uniqKey="Sugawara I" first="Isamu" last="Sugawara">Isamu Sugawara</name><name sortKey="Tone, Yukiko" sort="Tone, Yukiko" uniqKey="Tone Y" first="Yukiko" last="Tone">Yukiko Tone</name><name sortKey="Usui, Junko" sort="Usui, Junko" uniqKey="Usui J" first="Junko" last="Usui">Junko Usui</name><name sortKey="Watanabe, Hiroshi" sort="Watanabe, Hiroshi" uniqKey="Watanabe H" first="Hiroshi" last="Watanabe">Hiroshi Watanabe</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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