Prostate specific membrane antigen (PSMA) is a tissue-specific target for adenoviral transduction of prostate cancer in vitro

被引:18
作者
Kraaij, R
van Rijswijk, ALCT
Oomen, MHA
Haisma, HJ
Bangma, CH
机构
[1] Erasmus MC, Joseph Neikens Inst, Dept Urol, Sect Urol Oncol, NL-3000 DR Rotterdam, Netherlands
[2] Univ Groningen, Dept Therapeut Gene Modulat, Groningen, Netherlands
关键词
prostatic neoplasms; gene therapy; drug delivery systems; bispecific antibodies; surface antigens;
D O I
10.1002/pros.20150
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND. Adenovirus binds to the coxsackievirus and adenovirus receptor (CAR) as a first step in the process of cellular infection. This dependence on CAR potentially limits the use of adenovirus in gene therapy, since CAR is expressed in many tissues of the body, and, expression of CAR may be low or lost upon progression of certain tumors. These limitations maybe overcome by transductional targeting of adenovirus towards other cell surface molecules, We have evaluated the pantumoral epithelial cell adhesion molecule (EpCAM) anti prostate specific membrane antigen (PSMA) as possible targets for adenoviral transduction of prostate cancer cells. METHODS. Bispecific antibodies, constructed as conjugates between an anti-adenovirus fiber knob Fab' fragment and anti-EpCAM or anti-PSMA monoclonal antibodies, were incubated with an eGFP-expressing adenovirus to retarget this vector. A cell panel, that includes two Prostate cancer cell lines and four non-prostate control lines, Avere infected Nvith serial dilutions of the retargeted vector and specificity of infection was determined. RESULTS. Receptor-specific transduction was obtained for both EpCAM and PSMA. PSMA-retargeting was shown to be selective for the prostate cancer cell lines. CONCLUSIONS. PSMA serves as a tissue-specific target for adenoviral vectors and may be applicable for gene therapeutical treatment of prostate cancer. (C) 2004 Wiley-Liss, Inc.
引用
收藏
页码:253 / 259
页数:7
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