Cancer Vaccination by B7-1-Transfected Hepatocellular Carcinoma Cells

Abstract

Human hepatocellular carcinoma (HCC), one of the most common cancers, frequently recurs after primary therapy. A way to prevent this recurrence is needed. Enhanced immunity to some experimental tumors has been observed after transfection of the gene encoding the costimulatory molecule B7-1, a ligand for the CD28/cytolytic T-lymphocyte-associated antigen (CTLA) -4 counter receptor. However, it is not known whether the transfection of B7-1 gene into HCC cells could be useful for HCC treatment. To assess this, we introduced the B7-1 (CD80) gene into HCC cells. We investigated the expressions of B7-1, B7-2, and human leukocyte antigen (HLA) class I in seven human hepatocellular carcinoma (HCC) cell lines by flow cytometric analysis. Flow cytometric analysis revealed that they all expressed B7-1, B7-2, and HLA class I on the cell surface. However, the expression levels of B7-1 and B7-2 were very low while those of HLA class I were high. By human transfecting HCC cells with a plasmid containing human B7-1 cDNA, we were able to establish HCC cell lines strongly expressing B7-1. From mixed lymphocyte and tumor culture analysis, the primary cytolytic activity against parental HCC cells could be induced effectively by B7-1-transfected HCC cells. Furthermore, in the mouse tumor model, we found that overexpression of B7-1 on tumor cells can inhibit subcutaneous tumor development in syngeneic BALB/c mice. Vaccination with B7-1-transfected mouse HCC cells was effective as a tumor vaccine for preventing tumor development of parental HCC cells, and splenocytes from mice immunized with B7-1-transfected HCC cells showed cytolytic activity against parental HCC cells. Theses results demonstrate that vaccination of B7-1-transfected HCC cells can induce systemic immunity against parental HCC cells and suggest that vaccination of B7-1-transfected HCC cells may be therapeutically useful for suppressing HCC recurrence.