The “A, B and C” of Her-2 DNA vaccine development
Introduction The development of Her-2 DNA vaccine has progressed through three phases that can be categorized as phase “A”: the pursuit of Her-2 as a tumor-associated “antigen”, phase “B”: tilting the “balance” between tumor immunity and autoimmunity and phase “C”: the on-going “clinical trials”. Ma...
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| Veröffentlicht in: | Cancer Immunology, Immunotherapy Immunotherapy, 2008-11, Vol.57 (11), p.1711-1717 |
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| creator | Wei, Wei-Zen Jacob, Jennifer Radkevich-Brown, Olga Whittington, Paula Kong, Yi-chi M. |
| description | Introduction
The development of Her-2 DNA vaccine has progressed through three phases that can be categorized as phase “A”: the pursuit of Her-2 as a tumor-associated “antigen”, phase “B”: tilting the “balance” between tumor immunity and autoimmunity and phase “C”: the on-going “clinical trials”.
Materials and methods
In phase “A”, a panel of human ErbB-2 or Her-2 plasmids were constructed to encode non-transforming Her-2 derivatives. The immunogenicity and anti-tumor activity of Her-2 DNA vaccines were tested in human Her-2 transgenic mice with or without the depletion of regulatory T cells (Tregs). However, Treg depletion or other immune modulating regimens may increase the risk of autoimmunity. In phase “B”, the balance between tumor immunity and autoimmunity was assessed by monitoring the development of experimental autoimmune thyroiditis (EAT). To test the efficacy of Her-2 DNA vaccines in cancer patients, clinical trials have been initiated in phase “C”.
Results and conclusions
Significant anti-Her-2 and anti-tumor activity was observed when Her-2 transgenic mice were electro-vaccinated after Treg depletion. Susceptibility to EAT was also enhanced by Treg depletion and there was mutual amplification between Her-2 immunity and EAT development. Although Tregs regulate both EAT and Her-2 immunity, their effector mechanisms may differ. It may be possible to amplify tumor immunity with improved strategies that can by-pass undue autoimmunity. Critical information will be revealed in the next decade to expedite the development of cancer vaccines. |
| doi_str_mv | 10.1007/s00262-008-0464-y |
| format | Article |
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The development of Her-2 DNA vaccine has progressed through three phases that can be categorized as phase “A”: the pursuit of Her-2 as a tumor-associated “antigen”, phase “B”: tilting the “balance” between tumor immunity and autoimmunity and phase “C”: the on-going “clinical trials”.
Materials and methods
In phase “A”, a panel of human ErbB-2 or Her-2 plasmids were constructed to encode non-transforming Her-2 derivatives. The immunogenicity and anti-tumor activity of Her-2 DNA vaccines were tested in human Her-2 transgenic mice with or without the depletion of regulatory T cells (Tregs). However, Treg depletion or other immune modulating regimens may increase the risk of autoimmunity. In phase “B”, the balance between tumor immunity and autoimmunity was assessed by monitoring the development of experimental autoimmune thyroiditis (EAT). To test the efficacy of Her-2 DNA vaccines in cancer patients, clinical trials have been initiated in phase “C”.
Results and conclusions
Significant anti-Her-2 and anti-tumor activity was observed when Her-2 transgenic mice were electro-vaccinated after Treg depletion. Susceptibility to EAT was also enhanced by Treg depletion and there was mutual amplification between Her-2 immunity and EAT development. Although Tregs regulate both EAT and Her-2 immunity, their effector mechanisms may differ. It may be possible to amplify tumor immunity with improved strategies that can by-pass undue autoimmunity. Critical information will be revealed in the next decade to expedite the development of cancer vaccines.</description><identifier>ISSN: 0340-7004</identifier><identifier>EISSN: 1432-0851</identifier><identifier>DOI: 10.1007/s00262-008-0464-y</identifier><identifier>PMID: 18273615</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Animals ; Antigens ; Cancer Research ; Cancer vaccines ; Cancer Vaccines - immunology ; Cancer Vaccines - therapeutic use ; Clinical trials ; Clinical Trials as Topic ; Humans ; Immunology ; Kinases ; Lymphocytes ; Medicine ; Medicine & Public Health ; Neoplasms - immunology ; Neoplasms - therapy ; Oncology ; Peptides ; Proteins ; Receptor, ErbB-2 - genetics ; Symposium Paper ; T-Lymphocytes, Regulatory - immunology ; Transgenic animals ; Tumors ; Vaccines, DNA - immunology ; Vaccines, DNA - therapeutic use</subject><ispartof>Cancer Immunology, Immunotherapy, 2008-11, Vol.57 (11), p.1711-1717</ispartof><rights>Springer-Verlag 2008</rights><rights>Springer-Verlag 2008 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c498t-90faaf991bcca07449451dfbf229061c8c5f535ab0cf3950d25de0dd6c94f3d53</citedby><cites>FETCH-LOGICAL-c498t-90faaf991bcca07449451dfbf229061c8c5f535ab0cf3950d25de0dd6c94f3d53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3808248/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3808248/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,724,777,781,882,27905,27906,41469,42538,51300,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18273615$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wei, Wei-Zen</creatorcontrib><creatorcontrib>Jacob, Jennifer</creatorcontrib><creatorcontrib>Radkevich-Brown, Olga</creatorcontrib><creatorcontrib>Whittington, Paula</creatorcontrib><creatorcontrib>Kong, Yi-chi M.</creatorcontrib><title>The “A, B and C” of Her-2 DNA vaccine development</title><title>Cancer Immunology, Immunotherapy</title><addtitle>Cancer Immunol Immunother</addtitle><addtitle>Cancer Immunol Immunother</addtitle><description>Introduction
The development of Her-2 DNA vaccine has progressed through three phases that can be categorized as phase “A”: the pursuit of Her-2 as a tumor-associated “antigen”, phase “B”: tilting the “balance” between tumor immunity and autoimmunity and phase “C”: the on-going “clinical trials”.
Materials and methods
In phase “A”, a panel of human ErbB-2 or Her-2 plasmids were constructed to encode non-transforming Her-2 derivatives. The immunogenicity and anti-tumor activity of Her-2 DNA vaccines were tested in human Her-2 transgenic mice with or without the depletion of regulatory T cells (Tregs). However, Treg depletion or other immune modulating regimens may increase the risk of autoimmunity. In phase “B”, the balance between tumor immunity and autoimmunity was assessed by monitoring the development of experimental autoimmune thyroiditis (EAT). To test the efficacy of Her-2 DNA vaccines in cancer patients, clinical trials have been initiated in phase “C”.
Results and conclusions
Significant anti-Her-2 and anti-tumor activity was observed when Her-2 transgenic mice were electro-vaccinated after Treg depletion. Susceptibility to EAT was also enhanced by Treg depletion and there was mutual amplification between Her-2 immunity and EAT development. Although Tregs regulate both EAT and Her-2 immunity, their effector mechanisms may differ. It may be possible to amplify tumor immunity with improved strategies that can by-pass undue autoimmunity. Critical information will be revealed in the next decade to expedite the development of cancer vaccines.</description><subject>Animals</subject><subject>Antigens</subject><subject>Cancer Research</subject><subject>Cancer vaccines</subject><subject>Cancer Vaccines - immunology</subject><subject>Cancer Vaccines - therapeutic use</subject><subject>Clinical trials</subject><subject>Clinical Trials as Topic</subject><subject>Humans</subject><subject>Immunology</subject><subject>Kinases</subject><subject>Lymphocytes</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Neoplasms - immunology</subject><subject>Neoplasms - therapy</subject><subject>Oncology</subject><subject>Peptides</subject><subject>Proteins</subject><subject>Receptor, ErbB-2 - genetics</subject><subject>Symposium Paper</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>Transgenic animals</subject><subject>Tumors</subject><subject>Vaccines, DNA - immunology</subject><subject>Vaccines, DNA - therapeutic use</subject><issn>0340-7004</issn><issn>1432-0851</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkc1OGzEQx60K1ISUB-gFWRx6Yun4M-tLpZAWgoTaC5wtxx9k0WY3tZNIueVB2pfLk9QhERQkxMEaa-Y3_7Hnj9BnAucEoP81AVBJC4CyAC55sfqAuoSznCkFOUBdYByKPgDvoKOUHvKFglIfUYeUtM8kEV0kbiceb9Z_Bmf4ApvG4eFm_Re3AY98LCj-_nOAl8baqvHY-aWv29nUN_NP6DCYOvnjfeyhu8sft8NRcfPr6no4uCksV-W8UBCMCUqRsbUG-pwrLogL40CpAklsaUUQTJgx2MCUAEeF8-CctIoH5gTroW873dliPPXO5tHR1HoWq6mJK92aSr-sNNVE37dLzUooKS-zwJe9QGx_L3ya62mVrK9r0_h2kbRUXOYj3gWJkkoyBhk8fQU-tIvY5C1oSpggkjxCZAfZ2KYUfXh6MgG9tU7vrNPZOr21Tq9yz8n_f33u2HuVAboDUi419z4-T35b9R8XrqPF</recordid><startdate>20081101</startdate><enddate>20081101</enddate><creator>Wei, Wei-Zen</creator><creator>Jacob, Jennifer</creator><creator>Radkevich-Brown, Olga</creator><creator>Whittington, Paula</creator><creator>Kong, Yi-chi M.</creator><general>Springer-Verlag</general><general>Springer Nature B.V</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><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7QO</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20081101</creationdate><title>The “A, B and C” of Her-2 DNA vaccine development</title><author>Wei, Wei-Zen ; Jacob, Jennifer ; Radkevich-Brown, Olga ; Whittington, Paula ; Kong, Yi-chi M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c498t-90faaf991bcca07449451dfbf229061c8c5f535ab0cf3950d25de0dd6c94f3d53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Antigens</topic><topic>Cancer Research</topic><topic>Cancer vaccines</topic><topic>Cancer Vaccines - immunology</topic><topic>Cancer Vaccines - therapeutic use</topic><topic>Clinical trials</topic><topic>Clinical Trials as Topic</topic><topic>Humans</topic><topic>Immunology</topic><topic>Kinases</topic><topic>Lymphocytes</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Neoplasms - immunology</topic><topic>Neoplasms - therapy</topic><topic>Oncology</topic><topic>Peptides</topic><topic>Proteins</topic><topic>Receptor, ErbB-2 - genetics</topic><topic>Symposium Paper</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>Transgenic animals</topic><topic>Tumors</topic><topic>Vaccines, DNA - immunology</topic><topic>Vaccines, DNA - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wei, Wei-Zen</creatorcontrib><creatorcontrib>Jacob, Jennifer</creatorcontrib><creatorcontrib>Radkevich-Brown, Olga</creatorcontrib><creatorcontrib>Whittington, Paula</creatorcontrib><creatorcontrib>Kong, Yi-chi M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Biotechnology Research Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer Immunology, Immunotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wei, Wei-Zen</au><au>Jacob, Jennifer</au><au>Radkevich-Brown, Olga</au><au>Whittington, Paula</au><au>Kong, Yi-chi M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The “A, B and C” of Her-2 DNA vaccine development</atitle><jtitle>Cancer Immunology, Immunotherapy</jtitle><stitle>Cancer Immunol Immunother</stitle><addtitle>Cancer Immunol Immunother</addtitle><date>2008-11-01</date><risdate>2008</risdate><volume>57</volume><issue>11</issue><spage>1711</spage><epage>1717</epage><pages>1711-1717</pages><issn>0340-7004</issn><eissn>1432-0851</eissn><abstract>Introduction
The development of Her-2 DNA vaccine has progressed through three phases that can be categorized as phase “A”: the pursuit of Her-2 as a tumor-associated “antigen”, phase “B”: tilting the “balance” between tumor immunity and autoimmunity and phase “C”: the on-going “clinical trials”.
Materials and methods
In phase “A”, a panel of human ErbB-2 or Her-2 plasmids were constructed to encode non-transforming Her-2 derivatives. The immunogenicity and anti-tumor activity of Her-2 DNA vaccines were tested in human Her-2 transgenic mice with or without the depletion of regulatory T cells (Tregs). However, Treg depletion or other immune modulating regimens may increase the risk of autoimmunity. In phase “B”, the balance between tumor immunity and autoimmunity was assessed by monitoring the development of experimental autoimmune thyroiditis (EAT). To test the efficacy of Her-2 DNA vaccines in cancer patients, clinical trials have been initiated in phase “C”.
Results and conclusions
Significant anti-Her-2 and anti-tumor activity was observed when Her-2 transgenic mice were electro-vaccinated after Treg depletion. Susceptibility to EAT was also enhanced by Treg depletion and there was mutual amplification between Her-2 immunity and EAT development. Although Tregs regulate both EAT and Her-2 immunity, their effector mechanisms may differ. It may be possible to amplify tumor immunity with improved strategies that can by-pass undue autoimmunity. Critical information will be revealed in the next decade to expedite the development of cancer vaccines.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>18273615</pmid><doi>10.1007/s00262-008-0464-y</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancer Immunology, Immunotherapy, 2008-11, Vol.57 (11), p.1711-1717 |
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| source | MEDLINE; Springer Nature - Complete Springer Journals; PubMed Central |
| subjects | Animals Antigens Cancer Research Cancer vaccines Cancer Vaccines - immunology Cancer Vaccines - therapeutic use Clinical trials Clinical Trials as Topic Humans Immunology Kinases Lymphocytes Medicine Medicine & Public Health Neoplasms - immunology Neoplasms - therapy Oncology Peptides Proteins Receptor, ErbB-2 - genetics Symposium Paper T-Lymphocytes, Regulatory - immunology Transgenic animals Tumors Vaccines, DNA - immunology Vaccines, DNA - therapeutic use |
| title | The “A, B and C” of Her-2 DNA vaccine development |
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