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

The carbohydrate epitope, alpha Gal epitope, is known as a major xenoantige n. The epitope exists abundantly in non-primate mammals and has recently be en found on C-type retroviruses. Humans and Old World monkeys have anti-alp ha Gal antibody, a natural antibody. The present study was performed to exa mine if the aGal epitope could be used as a new target of gene therapy agai nst human cancer. Bovine alpha1-3 galactosyltransferase (alpha1-3 GT) cDNA which produces the alpha Gal epitope was electrophoretically transfected in to the human pancreatic cancer cell line, MIA PaCa-2 and the human hepatoce llular carcinoma cell line, huH7. The expression of the alpha Gal epitope w as confirmed by flow cytometry, using specific binding with IB4 lectin conj ugated with fluorescein isothiocyanate. Transfected MIA PaCa-2 cells and hu H7 cells showed a positive log shift for the aGal epitope. Next, we examine d whether human cancer cells expressing the alpha Gal epitope could be lyse d by natural antibodies using the complement-dependent cytotoxic cross-matc h test. The results showed that transfected MIA PaCa-2 cells and huH7 cells were effectively lysed by human natural antibodies, arid the killing was o bserved with any serum irrelevant of blood type. The results indicate that transfection of the functional alpha1-3 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. (C) 2001 Elsevier Science I reland Ltd. All rights reserved.