Cloning and expression of the tumor-associated antigen L6.
The L6 cell surface antigen, which is highly expressed on lung, breast, colon, and ovarian carcinomas, has attracted attention as a therapeutic target for murine monoclonal antibodies and their humanized counterparts. Its molecular nature has, however, remained elusive. Here we describe the expression cloning of a cDNA encoding the L6 antigen. COS cells transfected with this cDNA direct the expression of an approximately 24-kDa surface protein that reacts with the two anti-L6 monoclonal antibodies available. The predicted L6 peptide sequence is 202 amino acids long and contains three predicted NH2-terminal hydrophobic transmembrane regions, which are followed by a hydrophilic region containing two potential N-linked glycosylation sites and a COOH-terminal hydrophobic transmembrane region. The L6 antigen is related to a number of cell surface proteins with similar predicted membrane topology that have been implicated in cell growth. Two other members of this family of proteins, CD63 (ME491) and CO-029, are also highly expressed on tumor cells. The present findings should make it possible to further study the role of the L6-defined antigen in normal and neoplastic cells and to construct animal models for development of improved agents for active and passive cancer immunotherapy.
Marken
J S
JS
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121.
Schieven
G L
GL
Hellström
I
I
Hellström
K E
KE
Aruffo
A
A
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics*; D000954:Antigens, Surface / Q000032:analysis / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D003110:Colonic Neoplasms; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015723:Gene Library; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics*; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C074075:TM4SF1 protein, human