Liposome-mediated gene transfer into human basal cell carcinoma

被引:20
|
作者
Hottiger, MO
Dam, TN
Nickoloff, BJ
Johnson, TM
Nabel, GJ
机构
[1] Univ Michigan, Med Ctr, Howard Hughes Med Inst, Dept Internal Med, Ann Arbor, MI USA
[2] Univ Michigan, Med Ctr, Howard Hughes Med Inst, Dept Biol Chem, Ann Arbor, MI USA
[3] Univ Michigan, Med Ctr, Dept Dermatol Otorhinolaryngol & Surg, Ann Arbor, MI 48109 USA
[4] Loyola Univ, Med Ctr, Dept Pathol, Skin Canc Res Labs,Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA
关键词
antigen-presenting cells; basal cell carcinoma; cationic liposomes; gene therapy; interferon; lipoplexes;
D O I
10.1038/sj.gt.3301036
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Direct intralesional injection of DNA encoding interferon-alpha 2 (IFN-alpha 2) was used in an effort to sustain local protein delivery for the treatment of human basal cell carcinoma (BCC). A novel model to study this malignancy was established by transplantation of human BCC tissue on to immunodeficient mice with a relatively high rate of engraftment and stable phenotype for superficial BCC (20 of 25; 80%. Gene transfer was significantly increased by using DNA liposome complexes (lipoplexes). Recombinant gene expression was detected predominantly in the epidermis and, to a lesser extent, in the dermis. Gene transfer of IFN-alpha 2 using this method resulted in sustained production of IFN-alpha 2 protein and increased expression of a known IFN-inducible gene, the class II major histocompatibility (MHC) antigen, and induced BCC regression, presumably through a non-immune mechanism. Intralesional injection of DNA lipoplexes encoding IFN-alpha protein may therefore be applicable to the treatment of cutaneous BCC.
引用
收藏
页码:1929 / 1935
页数:7
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