Large Scale Identification of Human Hepatocellular Carcinoma-Associated Antigens by Autoantibodies

Abstract

Autoantibodies are often detected in hepatocellular carcinoma (HCC), and these responses may represent recognition of tumor Ags that are associated with transformation events. The identities of these Ags, however, are less well known. Using serological analysis of recombinant cDNA expression libraries (SEREX) from four HCC patients, we identified 55 independent cDNA sequences potentially encoding HCC tumor Ags. Of these genes, 15 are novel. Two such proteins, HCA587 and HCA661, were predominantly detected in testis, but not in other normal tissues, except for a weak expression in normal pancreas. In addition to HCC, these two Ags can be found in cancers of other histological types. Therefore, they can be categorized as cancer-testis (CT) Ags. Two other Ags (HCA519 and HCA90) were highly overexpressed in HCC and also expressed in cancer cell lines of lung, prostate, and pancreas, but not in the respective normal tissues. Four other Ags were identified to be expressed in particular types of cancer cell lines (HCA520 in an ovarian cancer cell line, HCA59 and HCA67 in a colon cancer cell line, HCA58 in colon and ovarian cancer cell lines), but not in the normal tissue counterpart(s). In addition, abundant expression of complement inactivation factors was found in HCC. These results indicate a broad range expression of autoantigens in HCC patients. Our findings open an avenue for the study of autoantigens in the transformation, metastasis, and immune evasion in HCC.

Transduction of dendritic cells with recombinant adenovirus encoding HCA661 activates autologous cytotoxic T lymphocytes to target hepatoma cells

“…The protein of HCA661 is immunogenic and capable of inducing an antibody response, as it was screened by SEREX from the serum of an HCC patient (Wang et al, 2002). HCA661 is a CT antigen, as it does not normally express in human tissues (except testis) and it expresses at 30% in HCC samples (Wang et al, 2002).…”

“…The protein of HCA661 is immunogenic and capable of inducing an antibody response, as it was screened by SEREX from the serum of an HCC patient (Wang et al, 2002). HCA661 is a CT antigen, as it does not normally express in human tissues (except testis) and it expresses at 30% in HCC samples (Wang et al, 2002). The potential of SEREX-defined CT antigens to induce cellular immunity despite a low frequency of antibodies in allogenic sera has been confirmed (Wang et al, 2002).…”

“…HCA661 is a CT antigen, as it does not normally express in human tissues (except testis) and it expresses at 30% in HCC samples (Wang et al, 2002). The potential of SEREX-defined CT antigens to induce cellular immunity despite a low frequency of antibodies in allogenic sera has been confirmed (Wang et al, 2002). The SEREX-defined NY-ESO-1 can induce a CTL response and the CTL-defined MAGEA-1 has also been identified by SEREX (Chen et al, 1998;Jager et al, 2000).…”

“…To subclone the human HCA661 cDNA, the plasmid pQE3.1/ HCA661 (Wang et al, 2002) was used as a template for polymerase chain reaction (PCR) using specific oligonucleotides encompassing the entire open reading frames. The following PCR primers were used: human Ad661 sense 5 0 -CGGAATTCATGGCAAAATATGTC AGT-3 0 , human Ad661 antisense 5 0 -GCTCTAGATTAGT-CATCCTCGTCATTC TC-3 0 .…”

“…HCA661 is a novel cancer/testis (CT) antigen screened by SEREX from sera of HCC patients (Wang et al, 2002). Cancer/testis antigens are predominantly expressed in cancer tissues, but not in normal counterparts except in germ cells in testis or ovary (Wang et al, 2002), which has made them very useful in vaccine-based immunotherapy (Rosenberg, 1999).…”