Photodynamic killing of human squamous cell carcinoma cells using a monoclonal antibody-photosensitizer conjugate |
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Authors: | F N Jiang D J Liu H Neyndorff M Chester S Y Jiang J G Levy |
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Affiliation: | Department of Microbiology, University of British Columbia, Vancouver, Canada. |
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Abstract: | We have developed procedures in which the photosensitizer benzoporphyrin derivative monoacid ring A (BPD) can be covalently linked to carrier molecules of modified polyvinyl alcohol (PVA) to produce water-soluble PVA-BPD conjugates with a molecular mass in the range of 30 kd. These carriers can subsequently be covalently linked to monoclonal antibodies (MoAbs) using heterobifunctional linking agents. We describe here such a conjugate in which the MoAb (5E8) has specificity for a glycoprotein detected on human squamous cell carcinomas of the lung. We provide evidence that the conjugates produced were covalently linked and retained both their photosensitizing and antigen-binding activities. We show further that the MoAb-PVA-BPD conjugate, in the presence of 10% fetal calf serum, exhibited highly enhanced phototoxic killing of the target cell line (A549) over that exhibited by free BPD or a control MoAb-PVA-BPD conjugate. These results demonstrate, therefore, both the selectivity and specificity of this MoAb conjugate. |
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