PHOTODYNAMIC KILLING OF HUMAN SQUAMOUS-CELL CARCINOMA-CELLS USING A MONOCLONAL ANTIBODY-PHOTOSENSITIZER CONJUGATE

被引:43
作者
JIANG, FN
LIU, DJ
NEYNDORFF, H
CHESTER, M
JIANG, SY
LEVY, JG
机构
[1] UNIV BRITISH COLUMBIA,DEPT MICROBIOL,300 6174 UNIV BLVD,VANCOUVER V6T 1Z3,BC,CANADA
[2] QUADRA LOG TECHNOL INC,VANCOUVER,BC,CANADA
[3] SHANGHAI MED UNIV,DEPT CHEM,SHANGHAI,PEOPLES R CHINA
基金
加拿大自然科学与工程研究理事会;
关键词
D O I
10.1093/jnci/83.17.1218
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:1218 / 1225
页数:8
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