Glycoprotein A34, a novel target for antibody-based cancer immunotherapy.
To identify novel, tissue-restricted cell surface proteins in cancer which can serve as targets for antibody-based diagnostics and therapeutics, a translated version of the expressed sequence tag database (tblastn) was mined for transcripts with similarity to the glycoprotein A33 (GPA33) colon cancer antigen. A novel human transcript, termed A34, was identified which encoded a putative cell surface protein, GPA34, which is approximately 30% identical to GPA33 and other members of the junctional adhesion molecule (JAM) family. Conventional end-point and quantitative real-time RT-PCR showed that A34 mRNA expression is highly tissue-restricted, as it is expressed predominantly in stomach and testis. A34 mRNA was also detected in 6/19 (31%) gastric cancers, 8/16 (50%) esophageal carcinomas, and 4/17 (23%) ovarian cancers, but not in lung, breast or colon carcinomas. A murine monoclonal antibody (mAb A34) was generated to the extracellular domain of the A34 protein and used to biochemically and immunohistochemically characterize the A34 antigenic system. The mAb A34 specifically recognized glycoproteins ranging in apparent size from 55-70 kDa, present in normal gastric mucosa and in COS-7 cells transfected with A34 cDNA. Of 31 different normal tissues examined by immunohistochemistry, GPA34 protein expression was detected primarily in normal stomach mucosa and testicular germ cells, and in the tumor cells of 5/17 (29%) gastric cancers, 7/11 (63%) esophageal cancers, and 2/21 (9%) ovarian cancers, in agreement with gene expression results. The A34 antigen and monoclonal antibody may be of considerable value for immunotherapy of different types of cancer.
Scanlan
Matthew J
MJ
Ludwig Institute for Cancer Research, New York Branch of Human Cancer Immunology at Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Ritter
Gerd
G
Yin
Beatrice W T
BW
Williams
Clarence
C
Cohen
Leonard S
LS
Coplan
Keren A
KA
Fortunato
Sheila R
SR
Frosina
Denise
D
Lee
Sang-Yull
SY
Murray
Anne E
AE
Chua
Ramon
R
Filonenko
Valeriy V
VV
Sato
Eiichi
E
Old
Lloyd J
LJ
Jungbluth
Achim A
AA
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000627:therapeutic use; D000937:Antigen-Antibody Reactions; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C510166:VSIG1 protein, human