Endogenous anti‐tumor antibody responses in nude mice
BACKGROUND Nude mice with xenografted human tumors is the most exploited animal model used to elucidate the efficacy of experimental radioimmunolocalization and radioimmunotherapy. These animals accept transplants and are generally considered immunologically inert with regard to cell‐mediated and hu...
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Published in | Cancer Vol. 80; no. S12; pp. 2404 - 2410 |
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Main Authors | , , , , , , , |
Format | Journal Article Conference Proceeding |
Language | English |
Published |
New York
John Wiley & Sons, Inc
15.12.1997
Wiley-Liss |
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Abstract | BACKGROUND
Nude mice with xenografted human tumors is the most exploited animal model used to elucidate the efficacy of experimental radioimmunolocalization and radioimmunotherapy. These animals accept transplants and are generally considered immunologically inert with regard to cell‐mediated and humoral immune responses against the tumors.
METHODS
Nude control mice and mice carrying human HeLa Hep‐2 tumor xenografts were studied for appearance of endogenous antibodies following inoculation with tumor cells. The titers of these antibodies were investigated by isotype‐specific enzyme‐linked immunosorbent assay (ELISA) technologies, fluorescence‐activated cell sorter analysis (FACS), BIAcore (Pharmacia Biosensor AB, Uppsala, Sweden) technology, and immunofluorescence.
RESULTS
The HeLa Hep‐2 cell line was found to be immunogenic in all investigated animals by means of ELISA, FACS, and BIAcore evaluations as well as by immunofluorescence against both tested antigens, placental alkaline phosphatase and cytokeratin 8. Predominantly immunoglobulin M antibodies were induced, but immunoglobulin G isotypes could also be identified. Sera from these tumor‐bearing mice were used for immunohistochemistry of the tumor cells. The antibodies seemed to be of low affinity and may be displaced by high‐affinity monoclonal antibodies used in radioimmunotargeting.
CONCLUSIONS
Nude mice bearing tumor xenografts produce significant amounts of antibodies against these two human tumor‐derived antigens. These endogenous antibodies may influence targeting of radiolabeled antibodies. They also have the potential to interfere with the pharmacokinetics of labeled or nonlabeled idiotypic antibodies during experimental immunolocalization. Cancer 1997; 80:2404‐10. © 1997 American Cancer Society.
Nude mice bearing tumor xenografts produce significant amounts of immunoglobulin G and M antibodies against two tumor cell‐derived human antigens, cytokeratin 8 and human placental alkaline phosphatase. |
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AbstractList | BACKGROUNDNude mice with xenografted human tumors is the most exploited animal model used to elucidate the efficacy of experimental radioimmunolocalization and radioimmunotherapy. These animals accept transplants and are generally considered immunologically inert with regard to cell-mediated and humoral immune responses against the tumors.METHODSNude control mice and mice carrying human HeLa Hep-2 tumor xenografts were studied for appearance of endogenous antibodies following inoculation with tumor cells. The titers of these antibodies were investigated by isotype-specific enzyme-linked immunosorbent assay (ELISA) technologies, fluorescence-activated cell sorter analysis (FACS), BIAcore (Pharmacia Biosensor AB, Uppsala, Sweden) technology, and immunofluorescence.RESULTSThe HeLa Hep-2 cell line was found to be immunogenic in all investigated animals by means of ELISA, FACS, and BIAcore evaluations as well as by immunofluorescence against both tested antigens, placental alkaline phosphatase and cytokeratin 8. Predominantly immunoglobulin M antibodies were induced, but immunoglobulin G isotypes could also be identified. Sera from these tumor-bearing mice were used for immunohistochemistry of the tumor cells. The antibodies seemed to be of low affinity and may be displaced by high-affinity monoclonal antibodies used in radioimmunotargeting.CONCLUSIONSNude mice bearing tumor xenografts produce significant amounts of antibodies against these two human tumor-derived antigens. These endogenous antibodies may influence targeting of radiolabeled antibodies. They also have the potential to interfere with the pharmacokinetics of labeled or nonlabeled idiotypic antibodies during experimental immunolocalization. BACKGROUND Nude mice with xenografted human tumors is the most exploited animal model used to elucidate the efficacy of experimental radioimmunolocalization and radioimmunotherapy. These animals accept transplants and are generally considered immunologically inert with regard to cell‐mediated and humoral immune responses against the tumors. METHODS Nude control mice and mice carrying human HeLa Hep‐2 tumor xenografts were studied for appearance of endogenous antibodies following inoculation with tumor cells. The titers of these antibodies were investigated by isotype‐specific enzyme‐linked immunosorbent assay (ELISA) technologies, fluorescence‐activated cell sorter analysis (FACS), BIAcore (Pharmacia Biosensor AB, Uppsala, Sweden) technology, and immunofluorescence. RESULTS The HeLa Hep‐2 cell line was found to be immunogenic in all investigated animals by means of ELISA, FACS, and BIAcore evaluations as well as by immunofluorescence against both tested antigens, placental alkaline phosphatase and cytokeratin 8. Predominantly immunoglobulin M antibodies were induced, but immunoglobulin G isotypes could also be identified. Sera from these tumor‐bearing mice were used for immunohistochemistry of the tumor cells. The antibodies seemed to be of low affinity and may be displaced by high‐affinity monoclonal antibodies used in radioimmunotargeting. CONCLUSIONS Nude mice bearing tumor xenografts produce significant amounts of antibodies against these two human tumor‐derived antigens. These endogenous antibodies may influence targeting of radiolabeled antibodies. They also have the potential to interfere with the pharmacokinetics of labeled or nonlabeled idiotypic antibodies during experimental immunolocalization. Cancer 1997; 80:2404‐10. © 1997 American Cancer Society. Nude mice bearing tumor xenografts produce significant amounts of immunoglobulin G and M antibodies against two tumor cell‐derived human antigens, cytokeratin 8 and human placental alkaline phosphatase. Nude mice with xenografted human tumors is the most exploited animal model used to elucidate the efficacy of experimental radioimmunolocalization and radioimmunotherapy. These animals accept transplants and are generally considered immunologically inert with regard to cell-mediated and humoral immune responses against the tumors. Nude control mice and mice carrying human HeLa Hep-2 tumor xenografts were studied for appearance of endogenous antibodies following inoculation with tumor cells. The titers of these antibodies were investigated by isotype-specific enzyme-linked immunosorbent assay (ELISA) technologies, fluorescence-activated cell sorter analysis (FACS), BIAcore (Pharmacia Biosensor AB, Uppsala, Sweden) technology, and immunofluorescence. The HeLa Hep-2 cell line was found to be immunogenic in all investigated animals by means of ELISA, FACS, and BIAcore evaluations as well as by immunofluorescence against both tested antigens, placental alkaline phosphatase and cytokeratin 8. Predominantly immunoglobulin M antibodies were induced, but immunoglobulin G isotypes could also be identified. Sera from these tumor-bearing mice were used for immunohistochemistry of the tumor cells. The antibodies seemed to be of low affinity and may be displaced by high-affinity monoclonal antibodies used in radioimmunotargeting. Nude mice bearing tumor xenografts produce significant amounts of antibodies against these two human tumor-derived antigens. These endogenous antibodies may influence targeting of radiolabeled antibodies. They also have the potential to interfere with the pharmacokinetics of labeled or nonlabeled idiotypic antibodies during experimental immunolocalization. |
Author | Sandström, Per Rathsman, Sandra Stigbrand, Torgny Ärlestig, Lisbeth Hietala, Sven‐Ola Norrlund, Rauni Rossi Ullén, Anders Åhlström, Katrine Riklund |
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References_xml | – volume: 37 start-page: 1845 year: 1989 end-page: 54 article-title: Diversity in immunoreactivity of tumor derived cytokeratin monoclonal antibodies publication-title: J Histochem Cytochem – volume: 11 start-page: 158 year: 1990 end-page: 66 article-title: Radioimmunolocalization in nude mice using anticytokeratin monoclonal antibodies publication-title: Tumor Biol – volume: 134 start-page: 1 year: 1991 end-page: 13 article-title: A polymer containing a repeating peptide sequence can stimulate T‐cell‐independent IgG antibody production in vivo publication-title: Cell Immunol – volume: 5 start-page: 234 year: 1992 end-page: 7 article-title: The choice of experimental models in cancer research: the key to ultimate success or failure? publication-title: NMR Biomed – start-page: 21 year: 1995 end-page: 31 – volume: 136 start-page: 1 year: 1983 end-page: 7 article-title: Antigenic determinants of human placental and testicular alkaline phosphatase as mapped by monoclonal antibodies publication-title: Eur J Biochem – volume: 1 start-page: 239 year: 1995 end-page: 44 article-title: Radioimmunotherapy of HeLa cell tumors in nude mice by a combination of iodidine‐131‐labeled monoclonal antibodies against placental alkaline phosphatase and cytokeratin publication-title: Tumor Targeting – volume: 55 start-page: 5868 year: 1995 end-page: 73 article-title: Use of anticytokeratin monoclonal anti‐idiotypic antibodies to improve tumor: nontumor ratio in experimental radioimmunolocalization publication-title: Cancer Res – volume: 32 start-page: 819 year: 1993 end-page: 24 article-title: Animal models for radiolabeled monoclonal antibodies in cancer research publication-title: Acta Oncol – volume: 136 start-page: 1 year: 1983 ident: 10.1002/(SICI)1097-0142(19971215)80:12+<2404::AID-CNCR11>3.0.CO;2-G-BIB5 publication-title: Eur J Biochem doi: 10.1111/j.1432-1033.1983.tb07697.x contributor: fullname: Millan – volume: 1 start-page: 239 year: 1995 ident: 10.1002/(SICI)1097-0142(19971215)80:12+<2404::AID-CNCR11>3.0.CO;2-G-BIB8 publication-title: Tumor Targeting contributor: fullname: Riklund Åhlström – volume: 5 start-page: 234 year: 1992 ident: 10.1002/(SICI)1097-0142(19971215)80:12+<2404::AID-CNCR11>3.0.CO;2-G-BIB1 publication-title: NMR Biomed doi: 10.1002/nbm.1940050507 contributor: fullname: Denekamp – volume: 11 start-page: 158 year: 1990 ident: 10.1002/(SICI)1097-0142(19971215)80:12+<2404::AID-CNCR11>3.0.CO;2-G-BIB7 publication-title: Tumor Biol doi: 10.1159/000217650 contributor: fullname: Sundström – volume: 134 start-page: 1 year: 1991 ident: 10.1002/(SICI)1097-0142(19971215)80:12+<2404::AID-CNCR11>3.0.CO;2-G-BIB4 publication-title: Cell Immunol doi: 10.1016/0008-8749(91)90326-7 contributor: fullname: Hillman – volume: 32 start-page: 819 year: 1993 ident: 10.1002/(SICI)1097-0142(19971215)80:12+<2404::AID-CNCR11>3.0.CO;2-G-BIB2 publication-title: Acta Oncol doi: 10.3109/02841869309096141 contributor: fullname: Aas – start-page: 21 volume-title: Cancer therapy with radiolabeled antibodies year: 1995 ident: 10.1002/(SICI)1097-0142(19971215)80:12+<2404::AID-CNCR11>3.0.CO;2-G-BIB3 contributor: fullname: Buchsbaum – volume: 37 start-page: 1845 year: 1989 ident: 10.1002/(SICI)1097-0142(19971215)80:12+<2404::AID-CNCR11>3.0.CO;2-G-BIB6 publication-title: J Histochem Cytochem doi: 10.1177/37.12.2479674 contributor: fullname: Sundström – volume: 55 start-page: 5868 year: 1995 ident: 10.1002/(SICI)1097-0142(19971215)80:12+<2404::AID-CNCR11>3.0.CO;2-G-BIB9 publication-title: Cancer Res contributor: fullname: Ullén |
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Snippet | BACKGROUND
Nude mice with xenografted human tumors is the most exploited animal model used to elucidate the efficacy of experimental radioimmunolocalization... Nude mice with xenografted human tumors is the most exploited animal model used to elucidate the efficacy of experimental radioimmunolocalization and... BACKGROUNDNude mice with xenografted human tumors is the most exploited animal model used to elucidate the efficacy of experimental radioimmunolocalization and... |
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SubjectTerms | Alkaline Phosphatase - immunology Animals Antibodies, Neoplasm - biosynthesis BIAcove Biological and medical sciences cytokeratin Enzyme-Linked Immunosorbent Assay Female Fluorescent Antibody Technique Humans immunoglobulin Keratins - immunology Medical sciences Mice Mice, Inbred BALB C Mice, Nude Neoplasm Transplantation Neoplasms, Experimental - immunology nude mice placental alkaline phosphatase Radiation therapy and radiosensitizing agent radioimmunolocalization radioimmunotherapy Transplantation, Heterologous Treatment with physical agents Treatment. General aspects Tumors |
Title | Endogenous anti‐tumor antibody responses in nude mice |
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