Expression of xenoantigen transformed human cancer cells to be susceptible to antibody-mediated cell killing

The carbohydrate epitope, αGal epitope, is known as a major xenoantigen. The epitope exists abundantly in non-primate mammals and has recently been found on C-type retroviruses. Humans and Old World monkeys have anti-αGal antibody, a natural antibody. The present study was performed to examine if the αGal epitope could be used as a new target of gene therapy against human cancer. Bovine α1–3 galactosyltransferase (α1–3 GT) cDNA which produces the αGal epitope was electrophoretically transfected into the human pancreatic cancer cell line, MIA PaCa-2 and the human hepatocellular carcinoma cell line, huH7. The expression of the αGal epitope was confirmed by flow cytometry, using specific binding with IB4 lectin conjugated with fluorescein isothiocyanate. Transfected MIA PaCa-2 cells and huH7 cells showed a positive log shift for the αGal epitope. Next, we examined whether human cancer cells expressing the αGal epitope could be lysed by natural antibodies using the complement-dependent cytotoxic cross-match test. The results showed that transfected MIA PaCa-2 cells and huH7 cells were effectively lysed by human natural antibodies, and the killing was observed with any serum irrelevant of blood type. The results indicate that transfection of the functional α1–3 GT gene into human cancer cells can lead to their transformation, making them susceptible to lysis by natural antibodies, and, thus, useful for gene therapy.