Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O76050 (neu)
 3,969 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have developed an efficient and cell-specific nonviral gene delivery system using monoclonal antibodies (mAb) coupled with branched 25-kDa polyethyleneimine (PEI). The system was evaluated for two model antibodies with different well-characterized antigen specificities: the mouse anti-human IgG1 mAb AS02 recognizing human CD90 (hThy-1) which is expressed on human fibroblasts, and the humanized anti-Her-2/neu mAb Trastuzumab recently introduced for the treatment of Her-2/neu-positive breast cancer. Efficacy and selectivity of gene delivery were evaluated for covalent mAb-PEI conjugates coupled with N-succinimidyl-3-(2-pyridyldithio)proprionate (SPDP) or N-succinimidyl-4-(maleimidomethyl)-cyclohexancarboxylate (SMCC), or, as a newly introduced coupling reagent, noncovalent complexes of mAb with 3-(2-(2-(vinylsulfonyl)ethylthio)ethyl)quinazoline-2,4(1H,3H)-dione (IBFB 110001) coupled to PEI. An enhanced green fluorescent protein (EGFP)-expressing reporter plasmid was used to monitor transfection efficiencies of cell lines expressing different levels of hCD90 or Her-2/neu. While mAb-PEI conjugates coupled with SPDP resulted in antigen-nonspecific EGFP expression, conjugates coupled with SMCC or IBFB 110001 enabled antigen-specific gene delivery. Thus, Her-2/neu-PEI conjugates prepared with IBFB 110001 allowed to transfect 23+/-2% of Her-2/neu-positive SKOV-3 versus 0.5+/-2% of Her-2/neu-negative MB-468 cells. Proof of principle for specific antibody-mediated gene transfer was demonstrated by saturating the Her-2/neu receptor with free anti-Her-2/neu, thereby blocking subsequent transfection with anti-Her-2/neu-PEI/DNA complexes.
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PMID:Monoclonal antibody-polyethyleneimine conjugates targeting Her-2/neu or CD90 allow cell type-specific nonviral gene delivery. 1568 Oct 94

Immunoconjugates of epirubicin were synthesized with monoclonal antibodies against the epidermal growth factor receptors, HER2/neu and EGFR, by creating a sulfhydryl-reactive epirubicin intermediate applying heterobifunctional succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC), which was introduced at alpha-monoamide groups of the epirubicin carbohydrate moiety. In parallel, N-succinimidyl-S-acetylthioacetate (SATA) was used to incorporate a sulfhydryl group into immunoglobulin at the terminal amine position of -lysine amino acid residues. Eprirubicin-SMCC-SATA-IgG immunoconjugates were produced by reacting epirubicin-SMCC and SATA-IgG at appropriate molar ratios. Epirubicin-(anti-HER2/neu) and epirubicin-(anti-EGFR) had greater potency against chemotherapeutic-resistant SKBr-3 mammary carcinoma than did epirubicin at epirubicin-equivalent concentrations. Epirubicin-(anti-HER2/neu) was more potent than epirubicin-(anti-EGFR), and a synergistic level of antineoplastic activity was detected with an epirubicin immunoconjugate 50/50 combination. Competitive P-glycoprotein inhibition with cyclosporin A or verapamil enhanced the potency of the epirubicin immunoconjugate 50/50 combination. Minor levels of antineoplastic activity were detected only with an immunoglobulin 50/50 combination of anti-HER2/neu and anti-EGFR. The investigations represent a potential strategy for enhancing the selective internalization, intracellular deposition, and antineoplastic potency of chemotherapeutics in multidrug-resistant neoplasias.
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PMID:Dual potency anti-HER2/neu and anti-EGFR anthracycline immunoconjugates in chemotherapeutic-resistant mammary carcinoma combined with cyclosporin A and verapamil P-glycoprotein inhibition. 1948 May 61