[Targeting delivery of therapeutic genes using monoclonal antibody; immunogene approach].
We are developing the "immunogene" system for the targeted delivery of therapeutic genes. The immunogene system utilizes the EGF receptor-mediated endocytosis. The Fab fragment of monoclonal antibody B4G7 against human EGF receptor was conjugated with polylysine to form an "Fab immunoporter", which forms an affinity complex with DNA. The transfection efficiency of Fab immunogene was approximately 10-fold higher than the Lipofectin. Gene transfer of HSV-tk gene into A431 tumor cells with Fab immunoporter was successful and the subsequent treatment with ganciclovir induced remarkable suicide effects conferring 1000-fold higher drug sensitivity. Thus, the immunogene system could be useful as a gene transfer vehicle targeting the EGF receptor-hyperproducing tumor cells.
Takayanagi
A
A
Department of Molecular Biology, Keio University School of Medicine.
Chen
J
J
Gamou
S
S
Shimizu
N
N
D000818:Animals; D000911:Antibodies, Monoclonal; D004247:DNA / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D004705:Endocytosis; D066246:ErbB Receptors / Q000276:immunology; D018390:Gene Targeting; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D009369:Neoplasms / Q000628:therapy; D011107:Polylysine
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D011107:Polylysine; D004247:DNA; D066246:ErbB Receptors