Primary research

Xenoantigen, an αGal epitope-expression construct driven by the hTERT-promoter, specifically kills human pancreatic cancer cell line

Tokihiko Sawada¹ , Osamu Yamada² , Naoko Yoshimura¹ , Keiko Hatori¹ , Shohei Fuchinoue¹ and Satoshi Teraoka¹

¹  Tokyo Women's Medical University, Kidney Center, Department of Surgery 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan

²  Tokyo Women's Medical University, Medical Research Institute 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan

author email corresponding author email

Cancer Cell International 2002, 2:14doi:10.1186/1475-2867-2-14

Published:	3 October 2002

Abstract

Background

We previously reported the usefulness of the αGal epitope as a target molecule for gene therapy against cancer. To induce cancer cell specific transcription of the αGal epitope, an expression vector which synthesizes the αGal epitope under the control of a promoter region of the human telomerase reverse transcriptase (hTERT), NK7, was constructed.

Methods

NK7 was transfected into a human pancreatic carcinoma cell line, MIA cells, and telomerase-negative SUSM-1 cells served controls. Expression of the αGal epitope was confirmed by flow cytometry using IB4 lectin. The susceptibility of transfected MIA cells to human natural antibodies, was examined using a complement-dependent cytotoxic cross-match test (CDC) and a flow cytometry using annexin V.

Results

The αGal epitope expression was detected only on the cell surfaces of NK7-transfected MIA cells, i.e., not on naive MIA cells or telomerase negative SUSM-1 cells. The CDC results indicated that MIA cells transfected with NK7 are susceptible to human natural antibody-mediated cell killing, and the differences, as compared to NK-7 transfected telomerase negative SUSM-1 cells or telomerase positive naïve MIA cells, were statistically significant. The flow cytometry using annexin V showed a higher number of the apoptotic cells in NK-7 transfected MIA cells than in naïve MIA cells.

Conclusions

The results suggest that αGal epitope-expression, under the control of the hTERT-promoter, may be useful in cancer specific gene therapy.