dioleoyl-phosphatidylethanolamine and Skin-Neoplasms

Patients with metastatic melanoma are immunosuppressed by the growing tumor. Allovectin-7 therapy is a form of active immunotherapy that aims at immunization of the host with substances designed to elicit an immune reaction that will eliminate or slow down the growth and spread of the cancer.. to describe the rationale for immunotherapy with Allovectin-7 and assess its safety profile and efficacy based on the results of completed melanoma clinical trials.. we reviewed both the published medical literature and the results of trials pending publication.. Allovectin-7 is a safe and active immunotherapeutic agent. It induces local and systemic durable responses in patients with metastatic melanoma.

Topics: Animals; beta 2-Microglobulin; Cancer Vaccines; Clinical Trials as Topic; DNA, Recombinant; Drug Screening Assays, Antitumor; Genetic Vectors; HLA-B7 Antigen; Humans; Immunotherapy, Active; Injections, Intralesional; Lipids; Lung Neoplasms; Macaca fascicularis; Melanoma; Mice; Phosphatidylethanolamines; Quaternary Ammonium Compounds; Skin Neoplasms; Tumor Escape; Vaccines, DNA

pH-sensitive drug carriers that are sensitive to the acidic (pH = ~6.5) microenvironments of tumor tissues have been primarily used as effective drug/gene/siRNA/microRNA carriers for releasing their payloads to tumor cells/tissues. Resistance to various drugs has become a big hurdle in systemic chemotherapy in cancer. Therefore delivery of chemotherapeutic agents and siRNA's targeting anti apoptotic genes possess advantages to overcome the efflux pump mediated and anti apoptosis-related drug resistance. Here, we report the development of nanocarrier system prepared from kojic acid backbone-based cationic amphiphile containing endosomal pH-sensitive imidazole ring. This pH-sensitive liposomal nanocarrier effectively delivers anti-cancer drug (Paclitaxel; PTX) and siRNA (Bcl-2), and significantly inhibits cell proliferation and reduces tumor growth. Tumor inhibition response attributes to the synergistic effect of PTX potency and MDR reversing ability of Bcl-2 siRNA in the tumor supporting that kojic acid based liposomal pH-sensitive nanocarrier as efficient vehicle for systemic co-delivery of drugs and siRNA.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Line, Tumor; Drug Compounding; Drug Delivery Systems; Gene Expression Regulation, Neoplastic; Hydrogen-Ion Concentration; Imidazoles; Liposomes; Melanoma, Experimental; Mice; Nanoparticles; Paclitaxel; Phosphatidylethanolamines; Proto-Oncogene Proteins c-bcl-2; Pyrones; RNA, Small Interfering; Skin Neoplasms; Tumor Burden

In this study, we developed a nonviral, cationic, targeted DNA-carrier system by coupling SAINT/DOPE lipids to monoclonal antibodies. The two monoclonal antibodies used were both tumor specific, that is, MOC31 recognizes the epithelial glycoprotein EGP-2 present in carcinomas and Herceptin recognizes the HER-2/neu protein in breast and ovarian cancers. Coupling was performed under nonreducing conditions by covalent attachment. The coupling procedure appeared to be reproducible and the binding capacity of the antibody was not affected by linking them to the cationic lipid. Binding and transfection efficiency was assayed with target cells and nontarget cells. SAINT/DOPE lipoplexes as such appeared to be an effective transfection reagent for various cell lines. After coupling SAINT/DOPE to the monoclonal antibodies or F(ab)2 fragments, it was shown that the targeted MoAb-SAINT/DOPE lipoplexes preferably bound to target cells, compared to binding to the nontarget cells, especially for the Herceptin-SAINT/DOPE lipoplexes. More importantly, transfection of the target cells could also be improved with these targeted lipoplexes. In conclusion, we have shown that by using monoclonal antibody-coupled SAINT/DOPE lipoplexes cells targeted gene delivery can be achieved, and also a higher number of transfected target cells was seen.

Topics: Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Cations; Cell Line, Tumor; DNA; Gene Targeting; Genetic Therapy; Humans; Immunoglobulin Fab Fragments; Lipid Metabolism; Liposomes; Melanoma; Mice; Neoplasms; Phosphatidylethanolamines; Plasmids; Skin Neoplasms; Transfection; Trastuzumab