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Human Cancer Biology |
Authors' Affiliations: 1 Ludwig Institute for Cancer Research, Melbourne Centre for Clinical Sciences, and 2 Department of Pathology, Austin Health, Heidelberg, Victoria, Australia; 3 Ludwig Institute for Cancer Research, Memorial Sloan Kettering Cancer Centre, and 4 Weill Cornell Medical College, New York, New York; and 5 Institute of Child Health, London, United Kingdom
Requests for reprints: Jonathan Cebon, Ludwig Institute for Cancer Research, Melbourne Centre for Clinical Sciences, Austin Health, Studley Road, Heidelberg, Victoria 3084, Australia. Phone: 61-3-9496-5462; Fax: 61-3-9457-6698; E-mail: Jonathan.cebon{at}ludwig.edu.au.
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/DPPA2 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/DPPA2 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/DPPA2 is a promising target for antigen-specific immunotherapy in NSCLC.
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M. Monk, M. Hitchins, and S. Hawes Differential expression of the embryo/cancer gene ECSA(DPPA2), the cancer/testis gene BORIS and the pluripotency structural gene OCT4, in human preimplantation development Mol. Hum. Reprod., June 1, 2008; 14(6): 347 - 355. [Abstract] [Full Text] [PDF] |
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