Use of circular dichroism spectroscopy in determining the conformation of a monoclonal antibody prior to its incorporation in an immunoliposome.

Attachment of antibodies to liposomes endows target specificity to liposomes for a certain cell or organ that express the targeted antigenic determinant. These so-called immunoliposomes hold high promise as targeted drug carriers. One approach of immunoliposome preparation involves conjugating antibodies to hydrophobic anchors (e.

Reversal of Vinca alkaloid resistance by anti-P-glycoprotein monoclonal antibody HYB-241 in a human tumor xenograft.

A panel of monoclonal antibodies (MAbs) to P-glycoprotein was developed by immunization of mice with multidrug-resistant human neuroepithelioma and neuroblastoma cells. All the anti-P-glycoprotein MAbs reacted with the extracellular portion of P-glycoprotein. The MAbs were examined for their ability to enhance accumulation of actinomycin D, vincristine, vinblastine, and doxorubicin in the human mdr1 transfectant cell line, BRO/pFRmdr1.

In vivo selection of human tumor cells resistant to monoclonal antibody-Vinca alkaloid immunoconjugates.

UCLA-P3 human lung adenocarcinoma cells were grown in nude mice and given repetitive treatments of a monoclonal antibody-Vinca alkaloid immunoconjugate. Although this therapy resulted in a greater than 4-fold reduction in mean tumor mass of the established tumors, some animals experienced a reinitiation of tumor growth after cessation of conjugate treatment. Two such animals were treated again with high doses of monoclonal antibody-Vinca but one of the tumors was no longer regressed by the drug conjugate.

Characterization of monoclonal antibodies recognizing a Mr 180,000 P-glycoprotein: differential expression of the Mr 180,000 and Mr 170,000 P-glycoproteins in multidrug-resistant human tumor cells.

P-glycoprotein is a plasma membrane protein believed to mediate resistance to natural product drugs such as vincristine, Adriamycin, and actinomycin D. To facilitate the study of human P-glycoprotein, monoclonal antibodies (designated HYB-612, HYB-241, and HYB-195) were raised against vincristine-resistant human neuroblastoma (SH-SY5Y/VCR) cells. The antibodies recognize a Mr 180,000 plasma membrane phosphoglycoprotein produced in increased amounts in SH-SY5Y/VCR as well as in vincristine-resistant human neuroepithelioma (MC-IXC/VCR), vinblastine-resistant human leukemia (CEM/VLB100), and actinomycin D- or vincristine-resistant Chinese hamster (DC-3F/AD X and DC-3F/VCRd-5L) cells, as compared to control cells.

Immunohistochemical analysis of pulmonary and pleural tumors with the monoclonal antibody HYB-612 directed against the multidrug resistance (MDR-1) gene product, P-glycoprotein.

In this study, 212 untreated primary pulmonary and pleural neoplasms were studied immunohistochemically with the monoclonal antibody HYB-612 which detects the multidrug resistance (MDR)-related P-glycoprotein (gp180). A tumor was considered positive for the expression of the MDR phenotype, even if a single rare positive cell was detected. Using this criterion, all of the various histologic subtypes were found to express MDR to varying degrees.