Mammaglobin-A cDNA vaccination of breast cancer patients induces antigen-specific cytotoxic CD4+ICOShi T cells
Mammaglobin-A (Mam-A) is a 10 kDa secretory protein that is overexpressed in 80 % of primary and metastatic human breast cancers. Previous studies from our laboratory demonstrated that Mam-A cDNA vaccine can induce Mam-A-specific CD8 T cell responses and mediate regression of human breast cancer xen...
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| Veröffentlicht in: | Breast cancer research and treatment 2013-02, Vol.138 (1), p.109-118 |
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| creator | Tiriveedhi, Venkataswarup Fleming, Timothy P. Goedegebuure, Peter S. Naughton, Michael Ma, Cynthia Lockhart, Craig Gao, Feng Gillanders, William E. Mohanakumar, T. |
| description | Mammaglobin-A (Mam-A) is a 10 kDa secretory protein that is overexpressed in 80 % of primary and metastatic human breast cancers. Previous studies from our laboratory demonstrated that Mam-A cDNA vaccine can induce Mam-A-specific CD8 T cell responses and mediate regression of human breast cancer xenografts in NOD/SCID mice. In this article, we present our results on a phase I clinical trial of a Mam-A cDNA vaccination in breast cancer patients with stage-IV metastatic disease, including the impact of vaccination on the expression of the inducible co-stimulator molecule (ICOS) on CD4 T cells. Specimens from seven patients with stage-IV metastatic cancer were available for these analyses. Patients were vaccinated with a Mam-A cDNA vaccine on days 0, 28, and 56, and immune responses were assessed at serial time points following vaccination. At 6 months following the first vaccination, flow cytometric analysis demonstrated a significant increase in the frequency of CD4+ICOS
hi
T cells from 5 ± 2 % pre-vaccination to 23 ± 4 % (
p
|
| doi_str_mv | 10.1007/s10549-012-2110-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3656506</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1314705088</sourcerecordid><originalsourceid>FETCH-LOGICAL-c402t-98ad6c391db495e5d7abd69512d5dccab1144733d3b3e7ece56a229dfe39256e3</originalsourceid><addsrcrecordid>eNp9kU1v1DAQhi0EokvhB3BBviBVQoaxHdvxBWm15aNSoQfK2XIcZ-sqsRc7qei_x6tdClw4jTXzzDvjeRF6SeEtBVDvCgXRaAKUEUYpEP0IrahQnChG1WO0AioVkS3IE_SslFsA0Ar0U3TCmFQtlWyF4hc7TXY7pi5Essbu_Osa31nnQrRzSBGnAXfZ2zJjZ6PzGe9q3se54BD7xfmCbZzD1kdSdt6FITjs7uc0p5_1tTlv3lxsrr7dBHyNnR_H8hw9GexY_ItjPEXfP3643nwml1efLjbrS-IaYDPRre2l45r2XaOFF72yXS-1oKwXvXO2o7RpFOc977hX3nkhLWO6HzzXTEjPT9H7g-5u6Sbfu7pxtqPZ5TDZfG-SDebfSgw3ZpvuDJdCCpBV4OwokNOPxZfZTKHsv2CjT0sxlNNGgYC2rSg9oC6nUrIfHsZQMHufzMEnU30ye5-Mrj2v_t7voeO3MRV4fQRscXYccr1-KH84JVoAuhdiB67UUtz6bG7TkmO97X-m_wIrzKxB</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1314705088</pqid></control><display><type>article</type><title>Mammaglobin-A cDNA vaccination of breast cancer patients induces antigen-specific cytotoxic CD4+ICOShi T cells</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Tiriveedhi, Venkataswarup ; Fleming, Timothy P. ; Goedegebuure, Peter S. ; Naughton, Michael ; Ma, Cynthia ; Lockhart, Craig ; Gao, Feng ; Gillanders, William E. ; Mohanakumar, T.</creator><creatorcontrib>Tiriveedhi, Venkataswarup ; Fleming, Timothy P. ; Goedegebuure, Peter S. ; Naughton, Michael ; Ma, Cynthia ; Lockhart, Craig ; Gao, Feng ; Gillanders, William E. ; Mohanakumar, T.</creatorcontrib><description>Mammaglobin-A (Mam-A) is a 10 kDa secretory protein that is overexpressed in 80 % of primary and metastatic human breast cancers. Previous studies from our laboratory demonstrated that Mam-A cDNA vaccine can induce Mam-A-specific CD8 T cell responses and mediate regression of human breast cancer xenografts in NOD/SCID mice. In this article, we present our results on a phase I clinical trial of a Mam-A cDNA vaccination in breast cancer patients with stage-IV metastatic disease, including the impact of vaccination on the expression of the inducible co-stimulator molecule (ICOS) on CD4 T cells. Specimens from seven patients with stage-IV metastatic cancer were available for these analyses. Patients were vaccinated with a Mam-A cDNA vaccine on days 0, 28, and 56, and immune responses were assessed at serial time points following vaccination. At 6 months following the first vaccination, flow cytometric analysis demonstrated a significant increase in the frequency of CD4+ICOS
hi
T cells from 5 ± 2 % pre-vaccination to 23 ± 4 % (
p
< 0.001), with a concomitant decrease in the frequency of CD4+FoxP3+ T cells (regulatory T cells [Treg]) from 19 ± 6 to 10 ± 5 % (
p
< 0.05). ELISpot analysis of CD4+ICOS
hi
sorted T cells demonstrated that following vaccination the cytokines produced by Mam-A-specific T cells switched from IL-10 (78 ± 21 spm pre-vaccination to 32 ± 14 spm 5 months post-vaccine
p
< 0.001) to IFN-γ (12 ± 6 spm pre-vaccination to 124 ± 31 spm 5 months post-vaccine
p
< 0.001). The ratio of CD4+ICOS
hi
T cells to CD4+FoxP3+ T cells increased from 0.37 ± 0.12 before vaccination to 2.3 ± 0.72 (
p
= 0.021) following vaccination. Further, these activated CD4+ICOS
hi
T cells induced preferential lysis of human breast cancer cells expressing Mam-A protein. We conclude that Mam-A cDNA vaccination is associated with specific expansion and activation of CD4+ICOS
hi
T cells, with a concomitant decrease in Treg frequency. These encouraging results strongly suggest that Mam-A cDNA vaccination can induce antitumor immunity in breast cancer patients.</description><identifier>ISSN: 0167-6806</identifier><identifier>EISSN: 1573-7217</identifier><identifier>DOI: 10.1007/s10549-012-2110-9</identifier><identifier>PMID: 22678162</identifier><identifier>CODEN: BCTRD6</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Biological and medical sciences ; Breast Neoplasms - immunology ; Breast Neoplasms - therapy ; Cancer Vaccines - administration & dosage ; Cancer Vaccines - genetics ; Cancer Vaccines - immunology ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - metabolism ; Clinical Trial ; DNA, Complementary ; Female ; Forkhead Transcription Factors - metabolism ; Gynecology. Andrology. Obstetrics ; Humans ; Inducible T-Cell Co-Stimulator Protein - metabolism ; Interferon-gamma - secretion ; Interleukin-10 - secretion ; Lymphocyte Count ; Mammaglobin A - genetics ; Mammaglobin A - immunology ; Mammary gland diseases ; Medical sciences ; Medicine ; Medicine & Public Health ; Multiple tumors. Solid tumors. Tumors in childhood (general aspects) ; Oncology ; T-Lymphocytes, Cytotoxic - immunology ; T-Lymphocytes, Cytotoxic - metabolism ; Tumors ; Vaccines, DNA - administration & dosage ; Vaccines, DNA - genetics ; Vaccines, DNA - immunology</subject><ispartof>Breast cancer research and treatment, 2013-02, Vol.138 (1), p.109-118</ispartof><rights>Springer Science+Business Media, LLC. 2012</rights><rights>2014 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c402t-98ad6c391db495e5d7abd69512d5dccab1144733d3b3e7ece56a229dfe39256e3</citedby><cites>FETCH-LOGICAL-c402t-98ad6c391db495e5d7abd69512d5dccab1144733d3b3e7ece56a229dfe39256e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10549-012-2110-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10549-012-2110-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,777,781,882,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27580019$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22678162$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tiriveedhi, Venkataswarup</creatorcontrib><creatorcontrib>Fleming, Timothy P.</creatorcontrib><creatorcontrib>Goedegebuure, Peter S.</creatorcontrib><creatorcontrib>Naughton, Michael</creatorcontrib><creatorcontrib>Ma, Cynthia</creatorcontrib><creatorcontrib>Lockhart, Craig</creatorcontrib><creatorcontrib>Gao, Feng</creatorcontrib><creatorcontrib>Gillanders, William E.</creatorcontrib><creatorcontrib>Mohanakumar, T.</creatorcontrib><title>Mammaglobin-A cDNA vaccination of breast cancer patients induces antigen-specific cytotoxic CD4+ICOShi T cells</title><title>Breast cancer research and treatment</title><addtitle>Breast Cancer Res Treat</addtitle><addtitle>Breast Cancer Res Treat</addtitle><description>Mammaglobin-A (Mam-A) is a 10 kDa secretory protein that is overexpressed in 80 % of primary and metastatic human breast cancers. Previous studies from our laboratory demonstrated that Mam-A cDNA vaccine can induce Mam-A-specific CD8 T cell responses and mediate regression of human breast cancer xenografts in NOD/SCID mice. In this article, we present our results on a phase I clinical trial of a Mam-A cDNA vaccination in breast cancer patients with stage-IV metastatic disease, including the impact of vaccination on the expression of the inducible co-stimulator molecule (ICOS) on CD4 T cells. Specimens from seven patients with stage-IV metastatic cancer were available for these analyses. Patients were vaccinated with a Mam-A cDNA vaccine on days 0, 28, and 56, and immune responses were assessed at serial time points following vaccination. At 6 months following the first vaccination, flow cytometric analysis demonstrated a significant increase in the frequency of CD4+ICOS
hi
T cells from 5 ± 2 % pre-vaccination to 23 ± 4 % (
p
< 0.001), with a concomitant decrease in the frequency of CD4+FoxP3+ T cells (regulatory T cells [Treg]) from 19 ± 6 to 10 ± 5 % (
p
< 0.05). ELISpot analysis of CD4+ICOS
hi
sorted T cells demonstrated that following vaccination the cytokines produced by Mam-A-specific T cells switched from IL-10 (78 ± 21 spm pre-vaccination to 32 ± 14 spm 5 months post-vaccine
p
< 0.001) to IFN-γ (12 ± 6 spm pre-vaccination to 124 ± 31 spm 5 months post-vaccine
p
< 0.001). The ratio of CD4+ICOS
hi
T cells to CD4+FoxP3+ T cells increased from 0.37 ± 0.12 before vaccination to 2.3 ± 0.72 (
p
= 0.021) following vaccination. Further, these activated CD4+ICOS
hi
T cells induced preferential lysis of human breast cancer cells expressing Mam-A protein. We conclude that Mam-A cDNA vaccination is associated with specific expansion and activation of CD4+ICOS
hi
T cells, with a concomitant decrease in Treg frequency. These encouraging results strongly suggest that Mam-A cDNA vaccination can induce antitumor immunity in breast cancer patients.</description><subject>Biological and medical sciences</subject><subject>Breast Neoplasms - immunology</subject><subject>Breast Neoplasms - therapy</subject><subject>Cancer Vaccines - administration & dosage</subject><subject>Cancer Vaccines - genetics</subject><subject>Cancer Vaccines - immunology</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>Clinical Trial</subject><subject>DNA, Complementary</subject><subject>Female</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Inducible T-Cell Co-Stimulator Protein - metabolism</subject><subject>Interferon-gamma - secretion</subject><subject>Interleukin-10 - secretion</subject><subject>Lymphocyte Count</subject><subject>Mammaglobin A - genetics</subject><subject>Mammaglobin A - immunology</subject><subject>Mammary gland diseases</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</subject><subject>Oncology</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>T-Lymphocytes, Cytotoxic - metabolism</subject><subject>Tumors</subject><subject>Vaccines, DNA - administration & dosage</subject><subject>Vaccines, DNA - genetics</subject><subject>Vaccines, DNA - immunology</subject><issn>0167-6806</issn><issn>1573-7217</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1v1DAQhi0EokvhB3BBviBVQoaxHdvxBWm15aNSoQfK2XIcZ-sqsRc7qei_x6tdClw4jTXzzDvjeRF6SeEtBVDvCgXRaAKUEUYpEP0IrahQnChG1WO0AioVkS3IE_SslFsA0Ar0U3TCmFQtlWyF4hc7TXY7pi5Essbu_Osa31nnQrRzSBGnAXfZ2zJjZ6PzGe9q3se54BD7xfmCbZzD1kdSdt6FITjs7uc0p5_1tTlv3lxsrr7dBHyNnR_H8hw9GexY_ItjPEXfP3643nwml1efLjbrS-IaYDPRre2l45r2XaOFF72yXS-1oKwXvXO2o7RpFOc977hX3nkhLWO6HzzXTEjPT9H7g-5u6Sbfu7pxtqPZ5TDZfG-SDebfSgw3ZpvuDJdCCpBV4OwokNOPxZfZTKHsv2CjT0sxlNNGgYC2rSg9oC6nUrIfHsZQMHufzMEnU30ye5-Mrj2v_t7voeO3MRV4fQRscXYccr1-KH84JVoAuhdiB67UUtz6bG7TkmO97X-m_wIrzKxB</recordid><startdate>20130201</startdate><enddate>20130201</enddate><creator>Tiriveedhi, Venkataswarup</creator><creator>Fleming, Timothy P.</creator><creator>Goedegebuure, Peter S.</creator><creator>Naughton, Michael</creator><creator>Ma, Cynthia</creator><creator>Lockhart, Craig</creator><creator>Gao, Feng</creator><creator>Gillanders, William E.</creator><creator>Mohanakumar, T.</creator><general>Springer US</general><general>Springer</general><scope>IQODW</scope><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20130201</creationdate><title>Mammaglobin-A cDNA vaccination of breast cancer patients induces antigen-specific cytotoxic CD4+ICOShi T cells</title><author>Tiriveedhi, Venkataswarup ; Fleming, Timothy P. ; Goedegebuure, Peter S. ; Naughton, Michael ; Ma, Cynthia ; Lockhart, Craig ; Gao, Feng ; Gillanders, William E. ; Mohanakumar, T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c402t-98ad6c391db495e5d7abd69512d5dccab1144733d3b3e7ece56a229dfe39256e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Biological and medical sciences</topic><topic>Breast Neoplasms - immunology</topic><topic>Breast Neoplasms - therapy</topic><topic>Cancer Vaccines - administration & dosage</topic><topic>Cancer Vaccines - genetics</topic><topic>Cancer Vaccines - immunology</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD4-Positive T-Lymphocytes - metabolism</topic><topic>Clinical Trial</topic><topic>DNA, Complementary</topic><topic>Female</topic><topic>Forkhead Transcription Factors - metabolism</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Inducible T-Cell Co-Stimulator Protein - metabolism</topic><topic>Interferon-gamma - secretion</topic><topic>Interleukin-10 - secretion</topic><topic>Lymphocyte Count</topic><topic>Mammaglobin A - genetics</topic><topic>Mammaglobin A - immunology</topic><topic>Mammary gland diseases</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Multiple tumors. Solid tumors. Tumors in childhood (general aspects)</topic><topic>Oncology</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>T-Lymphocytes, Cytotoxic - metabolism</topic><topic>Tumors</topic><topic>Vaccines, DNA - administration & dosage</topic><topic>Vaccines, DNA - genetics</topic><topic>Vaccines, DNA - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tiriveedhi, Venkataswarup</creatorcontrib><creatorcontrib>Fleming, Timothy P.</creatorcontrib><creatorcontrib>Goedegebuure, Peter S.</creatorcontrib><creatorcontrib>Naughton, Michael</creatorcontrib><creatorcontrib>Ma, Cynthia</creatorcontrib><creatorcontrib>Lockhart, Craig</creatorcontrib><creatorcontrib>Gao, Feng</creatorcontrib><creatorcontrib>Gillanders, William E.</creatorcontrib><creatorcontrib>Mohanakumar, T.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Breast cancer research and treatment</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tiriveedhi, Venkataswarup</au><au>Fleming, Timothy P.</au><au>Goedegebuure, Peter S.</au><au>Naughton, Michael</au><au>Ma, Cynthia</au><au>Lockhart, Craig</au><au>Gao, Feng</au><au>Gillanders, William E.</au><au>Mohanakumar, T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mammaglobin-A cDNA vaccination of breast cancer patients induces antigen-specific cytotoxic CD4+ICOShi T cells</atitle><jtitle>Breast cancer research and treatment</jtitle><stitle>Breast Cancer Res Treat</stitle><addtitle>Breast Cancer Res Treat</addtitle><date>2013-02-01</date><risdate>2013</risdate><volume>138</volume><issue>1</issue><spage>109</spage><epage>118</epage><pages>109-118</pages><issn>0167-6806</issn><eissn>1573-7217</eissn><coden>BCTRD6</coden><abstract>Mammaglobin-A (Mam-A) is a 10 kDa secretory protein that is overexpressed in 80 % of primary and metastatic human breast cancers. Previous studies from our laboratory demonstrated that Mam-A cDNA vaccine can induce Mam-A-specific CD8 T cell responses and mediate regression of human breast cancer xenografts in NOD/SCID mice. In this article, we present our results on a phase I clinical trial of a Mam-A cDNA vaccination in breast cancer patients with stage-IV metastatic disease, including the impact of vaccination on the expression of the inducible co-stimulator molecule (ICOS) on CD4 T cells. Specimens from seven patients with stage-IV metastatic cancer were available for these analyses. Patients were vaccinated with a Mam-A cDNA vaccine on days 0, 28, and 56, and immune responses were assessed at serial time points following vaccination. At 6 months following the first vaccination, flow cytometric analysis demonstrated a significant increase in the frequency of CD4+ICOS
hi
T cells from 5 ± 2 % pre-vaccination to 23 ± 4 % (
p
< 0.001), with a concomitant decrease in the frequency of CD4+FoxP3+ T cells (regulatory T cells [Treg]) from 19 ± 6 to 10 ± 5 % (
p
< 0.05). ELISpot analysis of CD4+ICOS
hi
sorted T cells demonstrated that following vaccination the cytokines produced by Mam-A-specific T cells switched from IL-10 (78 ± 21 spm pre-vaccination to 32 ± 14 spm 5 months post-vaccine
p
< 0.001) to IFN-γ (12 ± 6 spm pre-vaccination to 124 ± 31 spm 5 months post-vaccine
p
< 0.001). The ratio of CD4+ICOS
hi
T cells to CD4+FoxP3+ T cells increased from 0.37 ± 0.12 before vaccination to 2.3 ± 0.72 (
p
= 0.021) following vaccination. Further, these activated CD4+ICOS
hi
T cells induced preferential lysis of human breast cancer cells expressing Mam-A protein. We conclude that Mam-A cDNA vaccination is associated with specific expansion and activation of CD4+ICOS
hi
T cells, with a concomitant decrease in Treg frequency. These encouraging results strongly suggest that Mam-A cDNA vaccination can induce antitumor immunity in breast cancer patients.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>22678162</pmid><doi>10.1007/s10549-012-2110-9</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0167-6806 |
| ispartof | Breast cancer research and treatment, 2013-02, Vol.138 (1), p.109-118 |
| issn | 0167-6806 1573-7217 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3656506 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Biological and medical sciences Breast Neoplasms - immunology Breast Neoplasms - therapy Cancer Vaccines - administration & dosage Cancer Vaccines - genetics Cancer Vaccines - immunology CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism Clinical Trial DNA, Complementary Female Forkhead Transcription Factors - metabolism Gynecology. Andrology. Obstetrics Humans Inducible T-Cell Co-Stimulator Protein - metabolism Interferon-gamma - secretion Interleukin-10 - secretion Lymphocyte Count Mammaglobin A - genetics Mammaglobin A - immunology Mammary gland diseases Medical sciences Medicine Medicine & Public Health Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Oncology T-Lymphocytes, Cytotoxic - immunology T-Lymphocytes, Cytotoxic - metabolism Tumors Vaccines, DNA - administration & dosage Vaccines, DNA - genetics Vaccines, DNA - immunology |
| title | Mammaglobin-A cDNA vaccination of breast cancer patients induces antigen-specific cytotoxic CD4+ICOShi T cells |
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