Liposome-mediated gene transfer into human basal cell carcinoma.
Direct intralesional injection of DNA encoding interferon-alpha2 (IFN-alpha2) 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-alpha2 using this method resulted in sustained production of IFN-alpha2 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.
Hottiger
M O
MO
Howard Hughes Medical Institute, University of Michigan Medical Center, Departments of Internal Medicine and Biological Chemistry, Ann Arbor, MI, USA.
Dam
T N
TN
Nickoloff
B J
BJ
Johnson
T M
TM
Nabel
G J
GJ
D000328:Adult; D000368:Aged; D000818:Animals; D018949:Antigens, CD1 / Q000032:analysis; D002280:Basal Cell Carcinoma / Q000276:immunology / Q000628:therapy*; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D015552:Injections, Intralesional; D007370:Interferon Type I / Q000627:therapeutic use; D016898:Interferon-alpha / Q000235:genetics*; D008081:Liposomes; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*; D016896:Treatment Outcome
D018949:Antigens, CD1; D006684:HLA-DR Antigens; D007370:Interferon Type I; D016898:Interferon-alpha; D008081:Liposomes; D011994:Recombinant Proteins