ECSA/DPPA2 is an embryo-cancer antigen that is coexpressed with cancer-testis antigens in non-small cell lung cancer.
OBJECTIVE
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.


METHODS
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.
Ludwig Institute for Cancer Research, Melbourne Centre for Clinical Sciences, Victoria, Australia.
Thomas
T
John
Otavia L
OL
Caballero
Suzanne J
SJ
Svobodová
Alan
A
Kong
Ramon
R
Chua
Judy
J
Browning
Sheila
S
Fortunato
Siddhartha
S
Deb
Melinda
M
Hsu
Craig A
CA
Gedye
Ian D
ID
Davis
Nasser
N
Altorki
Andrew J
AJ
Simpson
Yao-Tseng
YT
Chen
Marilyn
M
Monk
Jonathan S
JS
Cebon
D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D018797:Cell Cycle Proteins; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism*; D009687:Nuclear Proteins / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors
D000951:Antigens, Neoplasm; D018797:Cell Cycle Proteins; C502836:DPPA2 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors