Definition of tumor-associated antigens in hepatocellular carcinoma

With an estimated annual incidence of about one million cases, hepatocellul ar carcinoma (HCC) is one of the most common neoplasms worldwide. Of all ma lignant diseases, it is the major cause of death in some regions of Africa and Asia. The pathogenic mechanisms responsible for HCC are not well define d, and therapeutic means, especially in inoperable HCCs, are still unsatisf actory and await improvement. In the quest for tumor antigens exploitable f or gene therapy, we studied immune responses in the contest of HCC. A cDNA library derived from a human HCC sample was screened using the SEREX approa ch. Nineteen distinct antigens reactive with autologous IgG were identified . Sequence analysis revealed three of the cDNA clones to code for hitherto unknown proteins and 16 known genes products. Proteins as diverse in functi on as LDH, albumin, and kinectin were found. Furthermore, proteins involved in the transcription/translation machinery had elicited an immune response in the autologous host. A panel of allogenic sera including sera from pati ents with hepatitis, liver cirrhosis, HCC, and other tumor entities, as wel l as sera from normal individuals, was used for frequency analysis of antib ody responses. Whereas allogenic sera of HCC patients detected most antigen s at a high percentage, control sera were rarely antibody-positive. The nat ure of the major fraction of antigens described here are linked to liver, T hus, our findings demonstrate not only the complexity of the humoral immune response against HCC, but may also offer new insight into mechanisms under lying transformation of the liver cell.