A human monoclonal antibody specific to placental alkaline phosphatase,a marker of ovarian cancer |
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Authors: | Niccolò Ravenni Marcel Weber Dario Neri |
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Affiliation: | Department of Chemistry and Applied Biosciences; Institute of Pharmaceutical Sciences; ETH Zurich; Zurich, Switzerland |
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Abstract: | Placental alkaline phosphatase (PLAP) is a promising ovarian cancer biomarker. Here, we describe the isolation, affinity-maturation and characterization of two fully human monoclonal antibodies (termed B10 and D9) able to bind to human PLAP with a dissociation constant (Kd) of 10 and 30 nM, respectively. The ability of B10 and D9 antibodies to recognize the native antigen was confirmed by Biacore analysis, FACS and immunofluorescence studies using ovarian cancer cell lines and freshly-frozen human tissues. A quantitative biodistribution study in nude mice revealed that the B10 antibody preferentially localizes to A431 tumors, following intravenous administration. Anti-PLAP antibodies may serve as a modular building blocks for the development of targeted therapeutic products, armed with cytotoxic drugs, radionuclides or cytokines as payloads. |
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Keywords: | placental alkaline phosphatase PLAP ALPP Regan isoenzyme ovarian carcinoma antibody phage technology |
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