Immunohistology of carcinoembryonic antigen (CEA)-expressing tumors grafted in nude mice after radioimmunotherapy with 131I-labeled bivalent hapten and anti-CEA x antihapten bispecific antibody.
Identifieur interne : 003C39 ( Main/Exploration ); précédent : 003C38; suivant : 003C40Immunohistology of carcinoembryonic antigen (CEA)-expressing tumors grafted in nude mice after radioimmunotherapy with 131I-labeled bivalent hapten and anti-CEA x antihapten bispecific antibody.
Auteurs : RBID : pubmed:10541361English descriptors
- KwdEn :
- Animals, Antibodies, Bispecific (therapeutic use), Carcinoembryonic Antigen (analysis), Carcinoembryonic Antigen (immunology), Colonic Neoplasms (pathology), Colonic Neoplasms (radiotherapy), Female, Haptens (immunology), Haptens (therapeutic use), Humans, Iodine Radioisotopes (therapeutic use), Mice, Mice, Nude, Neoplasm Transplantation, Neoplasms, Experimental (pathology), Neoplasms, Experimental (radiotherapy), Radioimmunotherapy, Thyroid Neoplasms (pathology), Thyroid Neoplasms (radiotherapy), Transplantation, Heterologous.
- MESH :
- chemical , analysis : Carcinoembryonic Antigen.
- chemical , immunology : Carcinoembryonic Antigen, Haptens.
- chemical , therapeutic use : Antibodies, Bispecific, Haptens, Iodine Radioisotopes.
- pathology : Colonic Neoplasms, Neoplasms, Experimental, Thyroid Neoplasms.
- radiotherapy : Colonic Neoplasms, Neoplasms, Experimental, Thyroid Neoplasms.
- Animals, Female, Humans, Mice, Mice, Nude, Neoplasm Transplantation, Radioimmunotherapy, Transplantation, Heterologous.
Abstract
We have developed a pretargeting strategy, called the Affinity Enhancement System (AES), which uses bispecific antibodies (BsF(ab')2) to target radiolabeled bivalent haptens to tumor cells. We performed several radioimmunotherapy (RIT) experiments in nude mice grafted with LS174T colon carcinoma or TT medullary thyroid cancer. Mice were treated with 131I-labeled di-DTPA-indium-tyrosyl-lysine bivalent hapten (75-112 MBq) administered 15-48 h after anti-CEA x anti-DTPA-indium BsF(ab')2. Immunohistological studies were performed on tumors at their minimal relative volume (TT), on stabilized tumor nodules (LS174T), and on regrowing tumors (TT and LS174T). Untreated tumors were used as controls. On microscopic examination, regrowing tumors (2 months posttherapy) were similar to untreated tumors with cells showing their respective typical morphology (large cells with a high nucleocytoplasmic ratio for TT, small and very undifferentiated cells for LS174T). However, regrowing tumors showed larger necrotic areas and a higher mitotic index correlated with Ki-67 antigen staining. Immunostaining for CEA was as strong as for controls. By contrast, the immunohistology of TT tumors at their minimal relative volume (1 month posttherapy) or of LS174T residual nodules (8 months posttherapy) showed decreased mitotic indices correlated with poor Ki-67 antigen staining. Some clusters of LS174T presented with features of glandular lumen, which suggested a more differentiated and less aggressive status. In TT tumors, CEA expression remained unchanged (80-100% membrane and cytoplasmic staining), whereas only 70% of the LS174T tumors were stained, with 58% loss of the membrane expression. Repeated treatment early after the tumor has reached its minimal relative volume should thus be efficient and improve the overall efficacy of AES RIT.
PubMed: 10541361
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Immunohistology of carcinoembryonic antigen (CEA)-expressing tumors grafted in nude mice after radioimmunotherapy with 131I-labeled bivalent hapten and anti-CEA x antihapten bispecific antibody.</title><author><name sortKey="Gautherot, E" uniqKey="Gautherot E">E Gautherot</name><affiliation wicri:level="1"><nlm:affiliation>Immunotech S.A., Marseille, France. egautherot@hotmail.com</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Immunotech S.A., Marseille</wicri:regionArea><placeName><region type="région">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Kraeber Bodere, F" uniqKey="Kraeber Bodere F">F Kraeber-Bodéré</name></author><author><name sortKey="Daniel, L" uniqKey="Daniel L">L Daniel</name></author><author><name sortKey="Fiche, M" uniqKey="Fiche M">M Fiche</name></author><author><name sortKey="Rouvier, E" uniqKey="Rouvier E">E Rouvier</name></author><author><name sortKey="Sai Maurel, C" uniqKey="Sai Maurel C">C Saï-Maurel</name></author><author><name sortKey="Thedrez, P" uniqKey="Thedrez P">P Thedrez</name></author><author><name sortKey="Chatal, J F" uniqKey="Chatal J">J F Chatal</name></author><author><name sortKey="Barbet, J" uniqKey="Barbet J">J Barbet</name></author></titleStmt><publicationStmt><date when="1999">1999</date><idno type="RBID">pubmed:10541361</idno><idno type="pmid">10541361</idno><idno type="wicri:Area/Main/Corpus">003E04</idno><idno type="wicri:Area/Main/Curation">003E04</idno><idno type="wicri:Area/Main/Exploration">003C39</idno></publicationStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antibodies, Bispecific (therapeutic use)</term><term>Carcinoembryonic Antigen (analysis)</term><term>Carcinoembryonic Antigen (immunology)</term><term>Colonic Neoplasms (pathology)</term><term>Colonic Neoplasms (radiotherapy)</term><term>Female</term><term>Haptens (immunology)</term><term>Haptens (therapeutic use)</term><term>Humans</term><term>Iodine Radioisotopes (therapeutic use)</term><term>Mice</term><term>Mice, Nude</term><term>Neoplasm Transplantation</term><term>Neoplasms, Experimental (pathology)</term><term>Neoplasms, Experimental (radiotherapy)</term><term>Radioimmunotherapy</term><term>Thyroid Neoplasms (pathology)</term><term>Thyroid Neoplasms (radiotherapy)</term><term>Transplantation, Heterologous</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Carcinoembryonic Antigen</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Carcinoembryonic Antigen</term><term>Haptens</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antibodies, Bispecific</term><term>Haptens</term><term>Iodine Radioisotopes</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Colonic Neoplasms</term><term>Neoplasms, Experimental</term><term>Thyroid Neoplasms</term></keywords><keywords scheme="MESH" qualifier="radiotherapy" xml:lang="en"><term>Colonic Neoplasms</term><term>Neoplasms, Experimental</term><term>Thyroid Neoplasms</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Female</term><term>Humans</term><term>Mice</term><term>Mice, Nude</term><term>Neoplasm Transplantation</term><term>Radioimmunotherapy</term><term>Transplantation, Heterologous</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We have developed a pretargeting strategy, called the Affinity Enhancement System (AES), which uses bispecific antibodies (BsF(ab')2) to target radiolabeled bivalent haptens to tumor cells. We performed several radioimmunotherapy (RIT) experiments in nude mice grafted with LS174T colon carcinoma or TT medullary thyroid cancer. Mice were treated with 131I-labeled di-DTPA-indium-tyrosyl-lysine bivalent hapten (75-112 MBq) administered 15-48 h after anti-CEA x anti-DTPA-indium BsF(ab')2. Immunohistological studies were performed on tumors at their minimal relative volume (TT), on stabilized tumor nodules (LS174T), and on regrowing tumors (TT and LS174T). Untreated tumors were used as controls. On microscopic examination, regrowing tumors (2 months posttherapy) were similar to untreated tumors with cells showing their respective typical morphology (large cells with a high nucleocytoplasmic ratio for TT, small and very undifferentiated cells for LS174T). However, regrowing tumors showed larger necrotic areas and a higher mitotic index correlated with Ki-67 antigen staining. Immunostaining for CEA was as strong as for controls. By contrast, the immunohistology of TT tumors at their minimal relative volume (1 month posttherapy) or of LS174T residual nodules (8 months posttherapy) showed decreased mitotic indices correlated with poor Ki-67 antigen staining. Some clusters of LS174T presented with features of glandular lumen, which suggested a more differentiated and less aggressive status. In TT tumors, CEA expression remained unchanged (80-100% membrane and cytoplasmic staining), whereas only 70% of the LS174T tumors were stained, with 58% loss of the membrane expression. Repeated treatment early after the tumor has reached its minimal relative volume should thus be efficient and improve the overall efficacy of AES RIT.</div></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">10541361</PMID><DateCreated><Year>1999</Year><Month>11</Month><Day>24</Day></DateCreated><DateCompleted><Year>1999</Year><Month>11</Month><Day>24</Day></DateCompleted><DateRevised><Year>2006</Year><Month>11</Month><Day>15</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">1078-0432</ISSN><JournalIssue CitedMedium="Print"><Volume>5</Volume><Issue>10 Suppl</Issue><PubDate><Year>1999</Year><Month>Oct</Month></PubDate></JournalIssue><Title>Clinical cancer research : an official journal of the American Association for Cancer Research</Title><ISOAbbreviation>Clin. Cancer Res.</ISOAbbreviation></Journal><ArticleTitle>Immunohistology of carcinoembryonic antigen (CEA)-expressing tumors grafted in nude mice after radioimmunotherapy with 131I-labeled bivalent hapten and anti-CEA x antihapten bispecific antibody.</ArticleTitle><Pagination><MedlinePgn>3177s-3182s</MedlinePgn></Pagination><Abstract><AbstractText>We have developed a pretargeting strategy, called the Affinity Enhancement System (AES), which uses bispecific antibodies (BsF(ab')2) to target radiolabeled bivalent haptens to tumor cells. We performed several radioimmunotherapy (RIT) experiments in nude mice grafted with LS174T colon carcinoma or TT medullary thyroid cancer. Mice were treated with 131I-labeled di-DTPA-indium-tyrosyl-lysine bivalent hapten (75-112 MBq) administered 15-48 h after anti-CEA x anti-DTPA-indium BsF(ab')2. Immunohistological studies were performed on tumors at their minimal relative volume (TT), on stabilized tumor nodules (LS174T), and on regrowing tumors (TT and LS174T). Untreated tumors were used as controls. On microscopic examination, regrowing tumors (2 months posttherapy) were similar to untreated tumors with cells showing their respective typical morphology (large cells with a high nucleocytoplasmic ratio for TT, small and very undifferentiated cells for LS174T). However, regrowing tumors showed larger necrotic areas and a higher mitotic index correlated with Ki-67 antigen staining. Immunostaining for CEA was as strong as for controls. By contrast, the immunohistology of TT tumors at their minimal relative volume (1 month posttherapy) or of LS174T residual nodules (8 months posttherapy) showed decreased mitotic indices correlated with poor Ki-67 antigen staining. Some clusters of LS174T presented with features of glandular lumen, which suggested a more differentiated and less aggressive status. In TT tumors, CEA expression remained unchanged (80-100% membrane and cytoplasmic staining), whereas only 70% of the LS174T tumors were stained, with 58% loss of the membrane expression. Repeated treatment early after the tumor has reached its minimal relative volume should thus be efficient and improve the overall efficacy of AES RIT.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Gautherot</LastName><ForeName>E</ForeName><Initials>E</Initials><Affiliation>Immunotech S.A., Marseille, France. egautherot@hotmail.com</Affiliation></Author><Author ValidYN="Y"><LastName>Kraeber-Bodéré</LastName><ForeName>F</ForeName><Initials>F</Initials></Author><Author ValidYN="Y"><LastName>Daniel</LastName><ForeName>L</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Fiche</LastName><ForeName>M</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Rouvier</LastName><ForeName>E</ForeName><Initials>E</Initials></Author><Author ValidYN="Y"><LastName>Saï-Maurel</LastName><ForeName>C</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Thedrez</LastName><ForeName>P</ForeName><Initials>P</Initials></Author><Author ValidYN="Y"><LastName>Chatal</LastName><ForeName>J F</ForeName><Initials>JF</Initials></Author><Author ValidYN="Y"><LastName>Barbet</LastName><ForeName>J</ForeName><Initials>J</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType>Journal Article</PublicationType><PublicationType>Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>UNITED STATES</Country><MedlineTA>Clin Cancer Res</MedlineTA><NlmUniqueID>9502500</NlmUniqueID><ISSNLinking>1078-0432</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Antibodies, Bispecific</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Carcinoembryonic Antigen</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Haptens</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance>Iodine Radioisotopes</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Antibodies, Bispecific</DescriptorName><QualifierName MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Carcinoembryonic Antigen</DescriptorName><QualifierName MajorTopicYN="Y">analysis</QualifierName><QualifierName MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Colonic Neoplasms</DescriptorName><QualifierName MajorTopicYN="N">pathology</QualifierName><QualifierName MajorTopicYN="N">radiotherapy</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Haptens</DescriptorName><QualifierName MajorTopicYN="N">immunology</QualifierName><QualifierName MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Iodine Radioisotopes</DescriptorName><QualifierName MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Mice</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Mice, Nude</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Neoplasm Transplantation</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Neoplasms, Experimental</DescriptorName><QualifierName MajorTopicYN="N">pathology</QualifierName><QualifierName MajorTopicYN="Y">radiotherapy</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="Y">Radioimmunotherapy</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Thyroid Neoplasms</DescriptorName><QualifierName MajorTopicYN="N">pathology</QualifierName><QualifierName MajorTopicYN="N">radiotherapy</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N">Transplantation, Heterologous</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>1999</Year><Month>10</Month><Day>29</Day></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>1999</Year><Month>10</Month><Day>29</Day><Hour>0</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>1999</Year><Month>10</Month><Day>29</Day><Hour>0</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">10541361</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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