Chimeric anti-TNF-α monoclonal antibody cA2 binds recombinant transmembrane TNF-α and activates immune effector functions

Results of clinical trials have indicated that cA2, a neutralizing mouse/human IgG1 chimeric anti-human TNF-α monoclonal antibody, may have therapeutic benefit for rheumatoid arthritis patients. Arthritic joints contain, in addition to elevated levels of soluble TNF-α, high numbers of CD4 +T cells a...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Cytokine (Philadelphia, Pa.) Pa.), 1995-04, Vol.7 (3), p.251-259
Hauptverfasser: Scallon, Bernard J., Moore, Maria Arevalo, Trinh, Han, Knight, David M., Ghrayeb, John
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 259
container_issue 3
container_start_page 251
container_title Cytokine (Philadelphia, Pa.)
container_volume 7
creator Scallon, Bernard J.
Moore, Maria Arevalo
Trinh, Han
Knight, David M.
Ghrayeb, John
description Results of clinical trials have indicated that cA2, a neutralizing mouse/human IgG1 chimeric anti-human TNF-α monoclonal antibody, may have therapeutic benefit for rheumatoid arthritis patients. Arthritic joints contain, in addition to elevated levels of soluble TNF-α, high numbers of CD4 +T cells and macrophages, cells known to express transmembrane TNF-α upon activation. For that reason, we sought to determine if cA2 binds to transmembrane TNF-α and what effects such binding may have on TNF-α-expressing cells. A cell line expressing a cell-surface, mutant form of transmembrane TNF-α was prepared for these studies. Analysis of these TNF +cells by flow cytometry, direct binding, and competitive binding assays showed that cA2 binds to the transmembrane form of TNF-α with high avidity. Binding of the IgG1 isotype of cA2, but not an IgG4 version of cA2, resulted in efficient killing of the TNF +cells by both antibody-dependent cellular toxicity and complement-dependent cytotoxicity effector mechanisms. These findings indicate that, in addition to blocking soluble TNF-α activity, cA2 can bind to transmembrane TNF-α in vitro and suggest that cA2 binding may lead to lysis of TNF-α-expressing cells in vivo.
doi_str_mv 10.1006/cyto.1995.0029
format Article
fullrecord <record><control><sourceid>elsevier_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1006_cyto_1995_0029</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1043466685700294</els_id><sourcerecordid>S1043466685700294</sourcerecordid><originalsourceid>FETCH-LOGICAL-c339t-c21162d659db697875c97894174f256edecb69b34d6d088fbcc3d5916f5e763c3</originalsourceid><addsrcrecordid>eNp1kMFKAzEQhoMotVav3oS8wNZks5ttjqVYFYpe6nnZncxipElKsi0Un8oX8ZnM2uLNy8zP_PMPw0fILWdTzpi8h0Pvp1ypcspYrs7ImDMls6TF-aALkRVSyktyFeMHY0yJqhqRUSULJopyTD4X78ZiMEAb15ts_bLMvr-o9c7Dxrtm8ztuvT5QmOe0NU5HGhC8TTJZtA-NixZtmzrSU7xxmjbQm33TY6TG2l3ysOsQeh9ot3PJ8y5ek4uu2US8OfUJeVs-rBdP2er18XkxX2UghOozyDmXuZal0q1U1awqIVVV8Kro8lKiRkjzVhRaajabdS2A0KXisiuxkgLEhEyPdyH4GAN29TYY24RDzVk9QKwHiPUAsR4gpsDdMbDdtRb13_qJWvJnRx_T13uDoY5g0AFqk9j0tfbmv9M_VnqEHQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Chimeric anti-TNF-α monoclonal antibody cA2 binds recombinant transmembrane TNF-α and activates immune effector functions</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Scallon, Bernard J. ; Moore, Maria Arevalo ; Trinh, Han ; Knight, David M. ; Ghrayeb, John</creator><creatorcontrib>Scallon, Bernard J. ; Moore, Maria Arevalo ; Trinh, Han ; Knight, David M. ; Ghrayeb, John</creatorcontrib><description>Results of clinical trials have indicated that cA2, a neutralizing mouse/human IgG1 chimeric anti-human TNF-α monoclonal antibody, may have therapeutic benefit for rheumatoid arthritis patients. Arthritic joints contain, in addition to elevated levels of soluble TNF-α, high numbers of CD4 +T cells and macrophages, cells known to express transmembrane TNF-α upon activation. For that reason, we sought to determine if cA2 binds to transmembrane TNF-α and what effects such binding may have on TNF-α-expressing cells. A cell line expressing a cell-surface, mutant form of transmembrane TNF-α was prepared for these studies. Analysis of these TNF +cells by flow cytometry, direct binding, and competitive binding assays showed that cA2 binds to the transmembrane form of TNF-α with high avidity. Binding of the IgG1 isotype of cA2, but not an IgG4 version of cA2, resulted in efficient killing of the TNF +cells by both antibody-dependent cellular toxicity and complement-dependent cytotoxicity effector mechanisms. These findings indicate that, in addition to blocking soluble TNF-α activity, cA2 can bind to transmembrane TNF-α in vitro and suggest that cA2 binding may lead to lysis of TNF-α-expressing cells in vivo.</description><identifier>ISSN: 1043-4666</identifier><identifier>EISSN: 1096-0023</identifier><identifier>DOI: 10.1006/cyto.1995.0029</identifier><identifier>PMID: 7640345</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; anti-TNF-α ; Antibodies, Monoclonal ; antibody-dependent cellular cytotoxicity ; Antigen-Antibody Reactions ; Base Sequence ; Complement System Proteins - immunology ; complement-dependent cytotoxicity ; Cytotoxicity, Immunologic ; Humans ; Infliximab ; Lymphocyte Activation ; Membrane Proteins - immunology ; Mice ; Molecular Sequence Data ; Recombinant Fusion Proteins - immunology ; Recombinant Proteins - immunology ; T-Lymphocytes, Regulatory - immunology ; transmembrane TNF-α ; Tumor Necrosis Factor-alpha - immunology</subject><ispartof>Cytokine (Philadelphia, Pa.), 1995-04, Vol.7 (3), p.251-259</ispartof><rights>1995 Academic Press</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c339t-c21162d659db697875c97894174f256edecb69b34d6d088fbcc3d5916f5e763c3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1043466685700294$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7640345$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Scallon, Bernard J.</creatorcontrib><creatorcontrib>Moore, Maria Arevalo</creatorcontrib><creatorcontrib>Trinh, Han</creatorcontrib><creatorcontrib>Knight, David M.</creatorcontrib><creatorcontrib>Ghrayeb, John</creatorcontrib><title>Chimeric anti-TNF-α monoclonal antibody cA2 binds recombinant transmembrane TNF-α and activates immune effector functions</title><title>Cytokine (Philadelphia, Pa.)</title><addtitle>Cytokine</addtitle><description>Results of clinical trials have indicated that cA2, a neutralizing mouse/human IgG1 chimeric anti-human TNF-α monoclonal antibody, may have therapeutic benefit for rheumatoid arthritis patients. Arthritic joints contain, in addition to elevated levels of soluble TNF-α, high numbers of CD4 +T cells and macrophages, cells known to express transmembrane TNF-α upon activation. For that reason, we sought to determine if cA2 binds to transmembrane TNF-α and what effects such binding may have on TNF-α-expressing cells. A cell line expressing a cell-surface, mutant form of transmembrane TNF-α was prepared for these studies. Analysis of these TNF +cells by flow cytometry, direct binding, and competitive binding assays showed that cA2 binds to the transmembrane form of TNF-α with high avidity. Binding of the IgG1 isotype of cA2, but not an IgG4 version of cA2, resulted in efficient killing of the TNF +cells by both antibody-dependent cellular toxicity and complement-dependent cytotoxicity effector mechanisms. These findings indicate that, in addition to blocking soluble TNF-α activity, cA2 can bind to transmembrane TNF-α in vitro and suggest that cA2 binding may lead to lysis of TNF-α-expressing cells in vivo.</description><subject>Animals</subject><subject>anti-TNF-α</subject><subject>Antibodies, Monoclonal</subject><subject>antibody-dependent cellular cytotoxicity</subject><subject>Antigen-Antibody Reactions</subject><subject>Base Sequence</subject><subject>Complement System Proteins - immunology</subject><subject>complement-dependent cytotoxicity</subject><subject>Cytotoxicity, Immunologic</subject><subject>Humans</subject><subject>Infliximab</subject><subject>Lymphocyte Activation</subject><subject>Membrane Proteins - immunology</subject><subject>Mice</subject><subject>Molecular Sequence Data</subject><subject>Recombinant Fusion Proteins - immunology</subject><subject>Recombinant Proteins - immunology</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>transmembrane TNF-α</subject><subject>Tumor Necrosis Factor-alpha - immunology</subject><issn>1043-4666</issn><issn>1096-0023</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMFKAzEQhoMotVav3oS8wNZks5ttjqVYFYpe6nnZncxipElKsi0Un8oX8ZnM2uLNy8zP_PMPw0fILWdTzpi8h0Pvp1ypcspYrs7ImDMls6TF-aALkRVSyktyFeMHY0yJqhqRUSULJopyTD4X78ZiMEAb15ts_bLMvr-o9c7Dxrtm8ztuvT5QmOe0NU5HGhC8TTJZtA-NixZtmzrSU7xxmjbQm33TY6TG2l3ysOsQeh9ot3PJ8y5ek4uu2US8OfUJeVs-rBdP2er18XkxX2UghOozyDmXuZal0q1U1awqIVVV8Kro8lKiRkjzVhRaajabdS2A0KXisiuxkgLEhEyPdyH4GAN29TYY24RDzVk9QKwHiPUAsR4gpsDdMbDdtRb13_qJWvJnRx_T13uDoY5g0AFqk9j0tfbmv9M_VnqEHQ</recordid><startdate>19950401</startdate><enddate>19950401</enddate><creator>Scallon, Bernard J.</creator><creator>Moore, Maria Arevalo</creator><creator>Trinh, Han</creator><creator>Knight, David M.</creator><creator>Ghrayeb, John</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>19950401</creationdate><title>Chimeric anti-TNF-α monoclonal antibody cA2 binds recombinant transmembrane TNF-α and activates immune effector functions</title><author>Scallon, Bernard J. ; Moore, Maria Arevalo ; Trinh, Han ; Knight, David M. ; Ghrayeb, John</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c339t-c21162d659db697875c97894174f256edecb69b34d6d088fbcc3d5916f5e763c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1995</creationdate><topic>Animals</topic><topic>anti-TNF-α</topic><topic>Antibodies, Monoclonal</topic><topic>antibody-dependent cellular cytotoxicity</topic><topic>Antigen-Antibody Reactions</topic><topic>Base Sequence</topic><topic>Complement System Proteins - immunology</topic><topic>complement-dependent cytotoxicity</topic><topic>Cytotoxicity, Immunologic</topic><topic>Humans</topic><topic>Infliximab</topic><topic>Lymphocyte Activation</topic><topic>Membrane Proteins - immunology</topic><topic>Mice</topic><topic>Molecular Sequence Data</topic><topic>Recombinant Fusion Proteins - immunology</topic><topic>Recombinant Proteins - immunology</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>transmembrane TNF-α</topic><topic>Tumor Necrosis Factor-alpha - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Scallon, Bernard J.</creatorcontrib><creatorcontrib>Moore, Maria Arevalo</creatorcontrib><creatorcontrib>Trinh, Han</creatorcontrib><creatorcontrib>Knight, David M.</creatorcontrib><creatorcontrib>Ghrayeb, John</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Cytokine (Philadelphia, Pa.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Scallon, Bernard J.</au><au>Moore, Maria Arevalo</au><au>Trinh, Han</au><au>Knight, David M.</au><au>Ghrayeb, John</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chimeric anti-TNF-α monoclonal antibody cA2 binds recombinant transmembrane TNF-α and activates immune effector functions</atitle><jtitle>Cytokine (Philadelphia, Pa.)</jtitle><addtitle>Cytokine</addtitle><date>1995-04-01</date><risdate>1995</risdate><volume>7</volume><issue>3</issue><spage>251</spage><epage>259</epage><pages>251-259</pages><issn>1043-4666</issn><eissn>1096-0023</eissn><abstract>Results of clinical trials have indicated that cA2, a neutralizing mouse/human IgG1 chimeric anti-human TNF-α monoclonal antibody, may have therapeutic benefit for rheumatoid arthritis patients. Arthritic joints contain, in addition to elevated levels of soluble TNF-α, high numbers of CD4 +T cells and macrophages, cells known to express transmembrane TNF-α upon activation. For that reason, we sought to determine if cA2 binds to transmembrane TNF-α and what effects such binding may have on TNF-α-expressing cells. A cell line expressing a cell-surface, mutant form of transmembrane TNF-α was prepared for these studies. Analysis of these TNF +cells by flow cytometry, direct binding, and competitive binding assays showed that cA2 binds to the transmembrane form of TNF-α with high avidity. Binding of the IgG1 isotype of cA2, but not an IgG4 version of cA2, resulted in efficient killing of the TNF +cells by both antibody-dependent cellular toxicity and complement-dependent cytotoxicity effector mechanisms. These findings indicate that, in addition to blocking soluble TNF-α activity, cA2 can bind to transmembrane TNF-α in vitro and suggest that cA2 binding may lead to lysis of TNF-α-expressing cells in vivo.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>7640345</pmid><doi>10.1006/cyto.1995.0029</doi><tpages>9</tpages></addata></record>
fulltext fulltext
identifier ISSN: 1043-4666
ispartof Cytokine (Philadelphia, Pa.), 1995-04, Vol.7 (3), p.251-259
issn 1043-4666
1096-0023
language eng
recordid cdi_crossref_primary_10_1006_cyto_1995_0029
source MEDLINE; Elsevier ScienceDirect Journals
subjects Animals
anti-TNF-α
Antibodies, Monoclonal
antibody-dependent cellular cytotoxicity
Antigen-Antibody Reactions
Base Sequence
Complement System Proteins - immunology
complement-dependent cytotoxicity
Cytotoxicity, Immunologic
Humans
Infliximab
Lymphocyte Activation
Membrane Proteins - immunology
Mice
Molecular Sequence Data
Recombinant Fusion Proteins - immunology
Recombinant Proteins - immunology
T-Lymphocytes, Regulatory - immunology
transmembrane TNF-α
Tumor Necrosis Factor-alpha - immunology
title Chimeric anti-TNF-α monoclonal antibody cA2 binds recombinant transmembrane TNF-α and activates immune effector functions
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T05%3A03%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-elsevier_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Chimeric%20anti-TNF-%CE%B1%20monoclonal%20antibody%20cA2%20binds%20recombinant%20transmembrane%20TNF-%CE%B1%20and%20activates%20immune%20effector%20functions&rft.jtitle=Cytokine%20(Philadelphia,%20Pa.)&rft.au=Scallon,%20Bernard%20J.&rft.date=1995-04-01&rft.volume=7&rft.issue=3&rft.spage=251&rft.epage=259&rft.pages=251-259&rft.issn=1043-4666&rft.eissn=1096-0023&rft_id=info:doi/10.1006/cyto.1995.0029&rft_dat=%3Celsevier_cross%3ES1043466685700294%3C/elsevier_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/7640345&rft_els_id=S1043466685700294&rfr_iscdi=true