ECSA/DPPA2 is an Embryo-Cancer Antigen that Is Coexpressed with Cancer-Testis Antigens in Non–Small Cell Lung Cancer

Purpose: Cancer cells recapitulate many behaviors of pluripotent embryonic cells such as unlimited proliferation, and the capacity to self-renew and to migrate. Embryo-cancer sequence A ( ECSA ), later named developmental pluripotency associated-2 ( DPPA2 ), is an embryonic gene initially isolated f...

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Veröffentlicht in:Clinical cancer research 2008-06, Vol.14 (11), p.3291-3298
Hauptverfasser: JOHN, Thomas, CABALLERO, Otavia L, DAVIS, Lan D, ALTORKI, Nasser, SIMPSON, Andrew J, CHEN, Yao-Tseng, MONK, Marilyn, CEBON, Jonathan S, SVOBODOVA, Suzanne J, KONG, Alan, CHUA, Ramon, BROWNING, Judy, FORTUNATO, Sheila, DEB, Siddhartha, HSU, Melinda, GEDYE, Craig A
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container_end_page 3298
container_issue 11
container_start_page 3291
container_title Clinical cancer research
container_volume 14
creator JOHN, Thomas
CABALLERO, Otavia L
DAVIS, Lan D
ALTORKI, Nasser
SIMPSON, Andrew J
CHEN, Yao-Tseng
MONK, Marilyn
CEBON, Jonathan S
SVOBODOVA, Suzanne J
KONG, Alan
CHUA, Ramon
BROWNING, Judy
FORTUNATO, Sheila
DEB, Siddhartha
HSU, Melinda
GEDYE, Craig A
description Purpose: Cancer cells recapitulate many behaviors of pluripotent embryonic cells such as unlimited proliferation, and the capacity to self-renew and to migrate. Embryo-cancer sequence A ( ECSA ), later named developmental pluripotency associated-2 ( DPPA2 ), is an embryonic gene initially isolated from pluripotent human preimplantation embryos. We hypothesized that ECSA/DPPA2 would be quiescent in most normal tissues but expressed in cancers and may therefore be a useful target for immunotherapy. Experimental Design: ECSA/DPPA 2 expression was examined in a panel of normal and tumor tissue by reverse transcription PCR, quantitative real-time PCR, and immunohistochemistry. A panel of 110 non–small cell lung cancers (NSCLC) were further investigated for the presence of ECSA/DPPA2 transcripts and several cancer testis antigens (CTA). Sera from 104 patients were analyzed for spontaneous ECSA/DPPA2 antibody production by ELISA and Western blot. Results: ECSA/DPPA 2 transcripts were limited to normal testis, placenta, bone marrow, thymus, and kidney but expressed in a variety of tumors most notably in 30% of NSCLC. Enrichment for CTAs in ECSA/DPPA2 -positive NSCLC was observed. Immunohistochemistry confirmed nuclear and cytoplasmic localization in subpopulations of cells with coexpression of the CTA MAGE-A3. Antibodies to recombinant ECSA/DPPA2 protein were detected in the sera of 4 of 104 patients with NSCLC but not in healthy controls. Conclusions: The restricted expression in normal tissues, expression in tumors with coexpression of CTAs, and spontaneous immunogenicity indicate that ECSA/DPPA 2 is a promising target for antigen-specific immunotherapy in NSCLC.
doi_str_mv 10.1158/1078-0432.CCR-07-1322
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Embryo-cancer sequence A ( ECSA ), later named developmental pluripotency associated-2 ( DPPA2 ), is an embryonic gene initially isolated from pluripotent human preimplantation embryos. We hypothesized that ECSA/DPPA2 would be quiescent in most normal tissues but expressed in cancers and may therefore be a useful target for immunotherapy. Experimental Design: ECSA/DPPA 2 expression was examined in a panel of normal and tumor tissue by reverse transcription PCR, quantitative real-time PCR, and immunohistochemistry. A panel of 110 non–small cell lung cancers (NSCLC) were further investigated for the presence of ECSA/DPPA2 transcripts and several cancer testis antigens (CTA). Sera from 104 patients were analyzed for spontaneous ECSA/DPPA2 antibody production by ELISA and Western blot. Results: ECSA/DPPA 2 transcripts were limited to normal testis, placenta, bone marrow, thymus, and kidney but expressed in a variety of tumors most notably in 30% of NSCLC. Enrichment for CTAs in ECSA/DPPA2 -positive NSCLC was observed. Immunohistochemistry confirmed nuclear and cytoplasmic localization in subpopulations of cells with coexpression of the CTA MAGE-A3. Antibodies to recombinant ECSA/DPPA2 protein were detected in the sera of 4 of 104 patients with NSCLC but not in healthy controls. 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Embryo-cancer sequence A ( ECSA ), later named developmental pluripotency associated-2 ( DPPA2 ), is an embryonic gene initially isolated from pluripotent human preimplantation embryos. We hypothesized that ECSA/DPPA2 would be quiescent in most normal tissues but expressed in cancers and may therefore be a useful target for immunotherapy. Experimental Design: ECSA/DPPA 2 expression was examined in a panel of normal and tumor tissue by reverse transcription PCR, quantitative real-time PCR, and immunohistochemistry. A panel of 110 non–small cell lung cancers (NSCLC) were further investigated for the presence of ECSA/DPPA2 transcripts and several cancer testis antigens (CTA). Sera from 104 patients were analyzed for spontaneous ECSA/DPPA2 antibody production by ELISA and Western blot. Results: ECSA/DPPA 2 transcripts were limited to normal testis, placenta, bone marrow, thymus, and kidney but expressed in a variety of tumors most notably in 30% of NSCLC. Enrichment for CTAs in ECSA/DPPA2 -positive NSCLC was observed. Immunohistochemistry confirmed nuclear and cytoplasmic localization in subpopulations of cells with coexpression of the CTA MAGE-A3. Antibodies to recombinant ECSA/DPPA2 protein were detected in the sera of 4 of 104 patients with NSCLC but not in healthy controls. 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Drug treatments</topic><topic>Pneumology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>tumor antigens</topic><topic>Tumors of the respiratory system and mediastinum</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>JOHN, Thomas</creatorcontrib><creatorcontrib>CABALLERO, Otavia L</creatorcontrib><creatorcontrib>DAVIS, Lan D</creatorcontrib><creatorcontrib>ALTORKI, Nasser</creatorcontrib><creatorcontrib>SIMPSON, Andrew J</creatorcontrib><creatorcontrib>CHEN, Yao-Tseng</creatorcontrib><creatorcontrib>MONK, Marilyn</creatorcontrib><creatorcontrib>CEBON, Jonathan S</creatorcontrib><creatorcontrib>SVOBODOVA, Suzanne J</creatorcontrib><creatorcontrib>KONG, Alan</creatorcontrib><creatorcontrib>CHUA, Ramon</creatorcontrib><creatorcontrib>BROWNING, Judy</creatorcontrib><creatorcontrib>FORTUNATO, Sheila</creatorcontrib><creatorcontrib>DEB, Siddhartha</creatorcontrib><creatorcontrib>HSU, Melinda</creatorcontrib><creatorcontrib>GEDYE, Craig A</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><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>JOHN, Thomas</au><au>CABALLERO, Otavia L</au><au>DAVIS, Lan D</au><au>ALTORKI, Nasser</au><au>SIMPSON, Andrew J</au><au>CHEN, Yao-Tseng</au><au>MONK, Marilyn</au><au>CEBON, Jonathan S</au><au>SVOBODOVA, Suzanne J</au><au>KONG, Alan</au><au>CHUA, Ramon</au><au>BROWNING, Judy</au><au>FORTUNATO, Sheila</au><au>DEB, Siddhartha</au><au>HSU, Melinda</au><au>GEDYE, Craig A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ECSA/DPPA2 is an Embryo-Cancer Antigen that Is Coexpressed with Cancer-Testis Antigens in Non–Small Cell Lung Cancer</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2008-06-01</date><risdate>2008</risdate><volume>14</volume><issue>11</issue><spage>3291</spage><epage>3298</epage><pages>3291-3298</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Purpose: Cancer cells recapitulate many behaviors of pluripotent embryonic cells such as unlimited proliferation, and the capacity to self-renew and to migrate. Embryo-cancer sequence A ( ECSA ), later named developmental pluripotency associated-2 ( DPPA2 ), is an embryonic gene initially isolated from pluripotent human preimplantation embryos. We hypothesized that ECSA/DPPA2 would be quiescent in most normal tissues but expressed in cancers and may therefore be a useful target for immunotherapy. Experimental Design: ECSA/DPPA 2 expression was examined in a panel of normal and tumor tissue by reverse transcription PCR, quantitative real-time PCR, and immunohistochemistry. A panel of 110 non–small cell lung cancers (NSCLC) were further investigated for the presence of ECSA/DPPA2 transcripts and several cancer testis antigens (CTA). Sera from 104 patients were analyzed for spontaneous ECSA/DPPA2 antibody production by ELISA and Western blot. Results: ECSA/DPPA 2 transcripts were limited to normal testis, placenta, bone marrow, thymus, and kidney but expressed in a variety of tumors most notably in 30% of NSCLC. Enrichment for CTAs in ECSA/DPPA2 -positive NSCLC was observed. Immunohistochemistry confirmed nuclear and cytoplasmic localization in subpopulations of cells with coexpression of the CTA MAGE-A3. Antibodies to recombinant ECSA/DPPA2 protein were detected in the sera of 4 of 104 patients with NSCLC but not in healthy controls. Conclusions: The restricted expression in normal tissues, expression in tumors with coexpression of CTAs, and spontaneous immunogenicity indicate that ECSA/DPPA 2 is a promising target for antigen-specific immunotherapy in NSCLC.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>18519755</pmid><doi>10.1158/1078-0432.CCR-07-1322</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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source MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection
subjects Antigens, Neoplasm - biosynthesis
Antineoplastic agents
Biological and medical sciences
Blotting, Western
Carcinoma, Non-Small-Cell Lung - metabolism
DPPA2
Enzyme-Linked Immunosorbent Assay
Gene Expression
Humans
immune responses to cancer
Immunohistochemistry
lung cancer
Lung Neoplasms - metabolism
Medical sciences
Nuclear Proteins - biosynthesis
Pharmacology. Drug treatments
Pneumology
Reverse Transcriptase Polymerase Chain Reaction
tumor antigens
Tumors of the respiratory system and mediastinum
title ECSA/DPPA2 is an Embryo-Cancer Antigen that Is Coexpressed with Cancer-Testis Antigens in Non–Small Cell Lung Cancer
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