Photodynamic killing of human squamous cell carcinoma cells using a monoclonal antibody-photosensitizer conjugate.
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.
Jiang
F N
FN
Department of Microbiology, University of British Columbia, Vancouver, Canada.
Liu
D J
DJ
Neyndorff
H
H
Chester
M
M
Jiang
S Y
SY
Levy
J G
JG
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002470:Cell Survival / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015394:Molecular Structure; D010778:Photochemotherapy / Q000379:methods*; D011142:Polyvinyl Alcohol / Q000737:chemistry / Q000494:pharmacology*; D011166:Porphyrins / Q000737:chemistry / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; D011142:Polyvinyl Alcohol