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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Published in:	Clinical cancer research Vol. 14; no. 11; pp. 3291 - 3298
Main Authors:	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
Format:	Journal Article
Language:	English
Published:	Philadelphia, PA American Association for Cancer Research 01-06-2008
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 Lung disease Embryo Cancer testis antigen Tumor associated antigen Respiratory disease Lung cancer Bronchus disease Malignant tumor non-small cell lung carcinoma Cancer
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1078-0432 1557-3265
DOI:	10.1158/1078-0432.CCR-07-1322