Existent T-cell and antibody immunity to HER-2/neu protein in patients with breast cancer
The HER-2/neu protooncogene is amplified and overexpressed in 20-40% of invasive breast cancers. HER-2/neu protein overexpression is associated with aggressive disease and is an independent predictor of poor prognosis in several subsets of patients. The protein may also be related to cancer formatio...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 1994-01, Vol.54 (1), p.16-20 |
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| container_title | Cancer research (Chicago, Ill.) |
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| creator | Disis, M L Calenoff, E McLaughlin, G Murphy, A E Chen, W Groner, B Jeschke, M Lydon, N McGlynn, E Livingston, R B |
| description | The HER-2/neu protooncogene is amplified and overexpressed in 20-40% of invasive breast cancers. HER-2/neu protein overexpression is associated with aggressive disease and is an independent predictor of poor prognosis in several subsets of patients. The protein may also be related to cancer formation, with overexpression being detectable in 50-60% of ductal carcinomas in situ. It has been suggested that it might be possible to develop specific T-cell therapy directed against proteins involved in malignant transformation. One question is whether normal proteins that are overexpressed are appropriate targets for therapeutic immune attack. This report demonstrates that some patients with HER-2/neu-positive breast cancers have both existent CD4+ helper/inducer T-cell immunity and antibody-mediated immunity to HER-2/neu protein. Initial studies performed on 20 premenopausal breast cancer patients identified antibodies to HER-2/neu in 11 individuals. Similar antibody responses have been found in some normal individuals. The patient with the greatest antibody response was studied in detail. In addition to a humoral immune response this patient had evidence of a significant proliferative T-cell response to the HER-2/neu protein and peptides. Similar T-cell responses have been detected in additional patients. It has been assumed that patients would be immunologically tolerant to HER-2/neu as a self-protein and that immunity might be difficult to generate. If immunity could be generated, the result might be destructive autoimmunity. The current data support the notion that HER-2/neu-specific immunity might be used in therapy without destroying normal tissue but also raises questions as to the role of existent immunity in immune surveillance and cancer progression. |
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HER-2/neu protein overexpression is associated with aggressive disease and is an independent predictor of poor prognosis in several subsets of patients. The protein may also be related to cancer formation, with overexpression being detectable in 50-60% of ductal carcinomas in situ. It has been suggested that it might be possible to develop specific T-cell therapy directed against proteins involved in malignant transformation. One question is whether normal proteins that are overexpressed are appropriate targets for therapeutic immune attack. This report demonstrates that some patients with HER-2/neu-positive breast cancers have both existent CD4+ helper/inducer T-cell immunity and antibody-mediated immunity to HER-2/neu protein. Initial studies performed on 20 premenopausal breast cancer patients identified antibodies to HER-2/neu in 11 individuals. Similar antibody responses have been found in some normal individuals. The patient with the greatest antibody response was studied in detail. In addition to a humoral immune response this patient had evidence of a significant proliferative T-cell response to the HER-2/neu protein and peptides. Similar T-cell responses have been detected in additional patients. It has been assumed that patients would be immunologically tolerant to HER-2/neu as a self-protein and that immunity might be difficult to generate. If immunity could be generated, the result might be destructive autoimmunity. The current data support the notion that HER-2/neu-specific immunity might be used in therapy without destroying normal tissue but also raises questions as to the role of existent immunity in immune surveillance and cancer progression.</description><identifier>ISSN: 0008-5472</identifier><identifier>PMID: 7505195</identifier><language>eng</language><publisher>United States</publisher><subject>3T3 Cells - immunology ; Amino Acid Sequence ; Animals ; Antibodies, Neoplasm - analysis ; Antibodies, Neoplasm - blood ; Biomarkers, Tumor - chemistry ; Biomarkers, Tumor - immunology ; Breast Neoplasms - blood ; Breast Neoplasms - immunology ; Epitopes - analysis ; Female ; Humans ; Lymphocyte Activation ; Mice ; Middle Aged ; Molecular Sequence Data ; Proto-Oncogene Proteins - chemistry ; Proto-Oncogene Proteins - immunology ; Receptor, Epidermal Growth Factor - chemistry ; Receptor, Epidermal Growth Factor - immunology ; Receptor, ErbB-2 ; T-Lymphocytes - immunology ; Tumor Cells, Cultured</subject><ispartof>Cancer research (Chicago, Ill.), 1994-01, Vol.54 (1), p.16-20</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7505195$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Disis, M L</creatorcontrib><creatorcontrib>Calenoff, E</creatorcontrib><creatorcontrib>McLaughlin, G</creatorcontrib><creatorcontrib>Murphy, A E</creatorcontrib><creatorcontrib>Chen, W</creatorcontrib><creatorcontrib>Groner, B</creatorcontrib><creatorcontrib>Jeschke, M</creatorcontrib><creatorcontrib>Lydon, N</creatorcontrib><creatorcontrib>McGlynn, E</creatorcontrib><creatorcontrib>Livingston, R B</creatorcontrib><title>Existent T-cell and antibody immunity to HER-2/neu protein in patients with breast cancer</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>The HER-2/neu protooncogene is amplified and overexpressed in 20-40% of invasive breast cancers. HER-2/neu protein overexpression is associated with aggressive disease and is an independent predictor of poor prognosis in several subsets of patients. The protein may also be related to cancer formation, with overexpression being detectable in 50-60% of ductal carcinomas in situ. It has been suggested that it might be possible to develop specific T-cell therapy directed against proteins involved in malignant transformation. One question is whether normal proteins that are overexpressed are appropriate targets for therapeutic immune attack. This report demonstrates that some patients with HER-2/neu-positive breast cancers have both existent CD4+ helper/inducer T-cell immunity and antibody-mediated immunity to HER-2/neu protein. Initial studies performed on 20 premenopausal breast cancer patients identified antibodies to HER-2/neu in 11 individuals. Similar antibody responses have been found in some normal individuals. The patient with the greatest antibody response was studied in detail. In addition to a humoral immune response this patient had evidence of a significant proliferative T-cell response to the HER-2/neu protein and peptides. Similar T-cell responses have been detected in additional patients. It has been assumed that patients would be immunologically tolerant to HER-2/neu as a self-protein and that immunity might be difficult to generate. If immunity could be generated, the result might be destructive autoimmunity. The current data support the notion that HER-2/neu-specific immunity might be used in therapy without destroying normal tissue but also raises questions as to the role of existent immunity in immune surveillance and cancer progression.</description><subject>3T3 Cells - immunology</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antibodies, Neoplasm - analysis</subject><subject>Antibodies, Neoplasm - blood</subject><subject>Biomarkers, Tumor - chemistry</subject><subject>Biomarkers, Tumor - immunology</subject><subject>Breast Neoplasms - blood</subject><subject>Breast Neoplasms - immunology</subject><subject>Epitopes - analysis</subject><subject>Female</subject><subject>Humans</subject><subject>Lymphocyte Activation</subject><subject>Mice</subject><subject>Middle Aged</subject><subject>Molecular Sequence Data</subject><subject>Proto-Oncogene Proteins - chemistry</subject><subject>Proto-Oncogene Proteins - immunology</subject><subject>Receptor, Epidermal Growth Factor - chemistry</subject><subject>Receptor, Epidermal Growth Factor - immunology</subject><subject>Receptor, ErbB-2</subject><subject>T-Lymphocytes - immunology</subject><subject>Tumor Cells, Cultured</subject><issn>0008-5472</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNotkE1LxDAQhnNQ1nX1Jwg5eQvmo0naoyzVFRYEWQ-eSr7KRtq0Nim6_94sW5iXmYFnXmbmCqwxxiXihaQ34DbG79xygvkKrCTPVcXX4Kv-8zG5kOABGdd1UAWblbwe7An6vp-DTyeYBrirPxB9Cm6G4zQk5wPMMark83CEvz4doZ6cigkaFYyb7sB1q7ro7pe8AZ8v9WG7Q_v317ft8x4dKZMJVVYYQQSnWhVWtwQTK6ix2jilBatsyYkuFNcVOWNa4tK20oiSKaWtLVq2AY8X37zWz-xianofz6eo4IY5NlIwKrGoMviwgLPunW3GyfdqOjXLL9g_k0FasQ</recordid><startdate>19940101</startdate><enddate>19940101</enddate><creator>Disis, M L</creator><creator>Calenoff, E</creator><creator>McLaughlin, G</creator><creator>Murphy, A E</creator><creator>Chen, W</creator><creator>Groner, B</creator><creator>Jeschke, M</creator><creator>Lydon, N</creator><creator>McGlynn, E</creator><creator>Livingston, R B</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>19940101</creationdate><title>Existent T-cell and antibody immunity to HER-2/neu protein in patients with breast cancer</title><author>Disis, M L ; Calenoff, E ; McLaughlin, G ; Murphy, A E ; Chen, W ; Groner, B ; Jeschke, M ; Lydon, N ; McGlynn, E ; Livingston, R B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h237t-9d6c61652ba4dbf101d62cdbceab639d851b4a5b91c616b708df7c683aabdd4f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>3T3 Cells - immunology</topic><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antibodies, Neoplasm - analysis</topic><topic>Antibodies, Neoplasm - blood</topic><topic>Biomarkers, Tumor - chemistry</topic><topic>Biomarkers, Tumor - immunology</topic><topic>Breast Neoplasms - blood</topic><topic>Breast Neoplasms - immunology</topic><topic>Epitopes - analysis</topic><topic>Female</topic><topic>Humans</topic><topic>Lymphocyte Activation</topic><topic>Mice</topic><topic>Middle Aged</topic><topic>Molecular Sequence Data</topic><topic>Proto-Oncogene Proteins - chemistry</topic><topic>Proto-Oncogene Proteins - immunology</topic><topic>Receptor, Epidermal Growth Factor - chemistry</topic><topic>Receptor, Epidermal Growth Factor - immunology</topic><topic>Receptor, ErbB-2</topic><topic>T-Lymphocytes - immunology</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Disis, M L</creatorcontrib><creatorcontrib>Calenoff, E</creatorcontrib><creatorcontrib>McLaughlin, G</creatorcontrib><creatorcontrib>Murphy, A E</creatorcontrib><creatorcontrib>Chen, W</creatorcontrib><creatorcontrib>Groner, B</creatorcontrib><creatorcontrib>Jeschke, M</creatorcontrib><creatorcontrib>Lydon, N</creatorcontrib><creatorcontrib>McGlynn, E</creatorcontrib><creatorcontrib>Livingston, R B</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Disis, M L</au><au>Calenoff, E</au><au>McLaughlin, G</au><au>Murphy, A E</au><au>Chen, W</au><au>Groner, B</au><au>Jeschke, M</au><au>Lydon, N</au><au>McGlynn, E</au><au>Livingston, R B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Existent T-cell and antibody immunity to HER-2/neu protein in patients with breast cancer</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>1994-01-01</date><risdate>1994</risdate><volume>54</volume><issue>1</issue><spage>16</spage><epage>20</epage><pages>16-20</pages><issn>0008-5472</issn><abstract>The HER-2/neu protooncogene is amplified and overexpressed in 20-40% of invasive breast cancers. HER-2/neu protein overexpression is associated with aggressive disease and is an independent predictor of poor prognosis in several subsets of patients. The protein may also be related to cancer formation, with overexpression being detectable in 50-60% of ductal carcinomas in situ. It has been suggested that it might be possible to develop specific T-cell therapy directed against proteins involved in malignant transformation. One question is whether normal proteins that are overexpressed are appropriate targets for therapeutic immune attack. This report demonstrates that some patients with HER-2/neu-positive breast cancers have both existent CD4+ helper/inducer T-cell immunity and antibody-mediated immunity to HER-2/neu protein. Initial studies performed on 20 premenopausal breast cancer patients identified antibodies to HER-2/neu in 11 individuals. Similar antibody responses have been found in some normal individuals. The patient with the greatest antibody response was studied in detail. In addition to a humoral immune response this patient had evidence of a significant proliferative T-cell response to the HER-2/neu protein and peptides. Similar T-cell responses have been detected in additional patients. It has been assumed that patients would be immunologically tolerant to HER-2/neu as a self-protein and that immunity might be difficult to generate. If immunity could be generated, the result might be destructive autoimmunity. The current data support the notion that HER-2/neu-specific immunity might be used in therapy without destroying normal tissue but also raises questions as to the role of existent immunity in immune surveillance and cancer progression.</abstract><cop>United States</cop><pmid>7505195</pmid><tpages>5</tpages></addata></record> |
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| subjects | 3T3 Cells - immunology Amino Acid Sequence Animals Antibodies, Neoplasm - analysis Antibodies, Neoplasm - blood Biomarkers, Tumor - chemistry Biomarkers, Tumor - immunology Breast Neoplasms - blood Breast Neoplasms - immunology Epitopes - analysis Female Humans Lymphocyte Activation Mice Middle Aged Molecular Sequence Data Proto-Oncogene Proteins - chemistry Proto-Oncogene Proteins - immunology Receptor, Epidermal Growth Factor - chemistry Receptor, Epidermal Growth Factor - immunology Receptor, ErbB-2 T-Lymphocytes - immunology Tumor Cells, Cultured |
| title | Existent T-cell and antibody immunity to HER-2/neu protein in patients with breast cancer |
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