Immunological approach to hepatocellular carcinoma.
A library of monoclonal antibodies (MoAbs) has been produced against a human hepatocellular carcinoma (HCC) cell line designated FOCUS in order to study the antigenic properties of transformed hepatocytes. Several monoclonal antibodies (MoAbs) were initially selected for study since they bound to antigens which were overexpressed in HCC tissues compared with the adjacent uninvolved normal liver counterpart; in addition, these MoAbs revealed low level antigen expression on other normal human tissues. Subsequently, HCC cell lines were metabolically labelled and the antigens further characterized by immunoprecipitation and Western blot analysis. If the MoAb recognized a primary linear epitope on a protein, cloning was performed using a lambda GT11 cDNA expression library prepared from the FOCUS HCC cell line. These studies characterized the HCC associated antigen(s) at the molecular level. This review illustrates the value of such an experimental approach to search for and identify HCC associated antigens and emphasizes the biological properties of novel proteins may be defined and characterized by these techniques. More important, our investigations have described unique proteins that may not only be important in the pathogenesis of HCC but also demonstrates how such antigen-antibody systems may be used to develop strategies for immunotargetting and gene therapy of HCC.
Wands
J R
JR
Molecular Hepatology Laboratory, Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.
Lavaissiere
L
L
Moradpour
D
D
de la Monte
S
S
Mohr
L
L
Nicolau
C
C
Tanaka
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D002412:Cations; D003001:Cloning, Molecular; D018014:Gene Transfer Techniques; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D008081:Liposomes; D051379:Mice; D008819:Mice, Nude; D006899:Mixed Function Oxygenases / Q000235:genetics; D010641:Phenotype; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D002412:Cations; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D008081:Liposomes; D010750:Phosphoproteins; D006899:Mixed Function Oxygenases; C058291:aspartic acid 2-oxoglutarate-dependent dioxygenase