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Photoimmunotherapy of Human Ovarian Carcinoma Cells ex Vivo¹

Wellman Laboratories of Photomedicine, Vincent Gynecology Service [B. G.], and the Department of Dermatology [M. B., T. H.], Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

Photodynamic therapy is a relatively new and potentially selective experimental approach to the treatment of malignant neoplasms. Its inherent dual selectivity is reinforced by the use of photosensitizer-monoclonal antibody conjugates. The goal of this study was to evaluate the phototoxicity and selectivity of an immunoconjugate (IC) synthesized from a chlorin derivative chlorin e₆-monoethylenediamine monoamide (CMA) as the photosensitizer and an anti-ovarian carcinoma monoclonal antibody OC125. Binding efficiency and specificity of the IC were determined by enzyme-linked immunosorbent assay, and specific covalent linkage of the monoclonal antibody to the photosensitizer was demonstrated by fluorescence and electrophoresis. Phototoxicity was tested against ascites or pleural fluid cells from 15 patients with ovarian and nonovarian cancers. Tumor cells from the fluid were treated with the IC at 3 µM equivalent CMA concentration and irradiated at 654 nm (_max CMA in IC) at 25 J/cm² from an argon ion-pumped dye laser. Phototoxic efficacy was assayed by [³H]thymidine incorporation. Ovarian cancer cells exhibited high cytotoxicity with [³H]thymidine incorporation of 2.4 ± 2.2%, while nonovarian cancer cells under identical conditions exhibited none to reduced cytotoxicity with [³H]thymidine incorporation of 70 ± 54%. Using a Wilcoxon test, there was a statistically significant difference between these two groups (P < 0.001). Dose-response curves revealed reciprocity in photosensitizer concentration and fluence. These results demonstrate that photoimmunoconjugates retain significant antigen binding specificity and affinity, are effective in the selective photochemical eradication of target cells, and merit further evaluation as photochemotherapeutic agents.

¹ Supported in part by Office of Naval Research Grant N00014-86-K117, NIH Grant R01-AR40352, the Whitaker Foundation, the Milton Fund (Harvard University), and Vincent Memorial Hospital.

² To whom requests for reprints should be addressed.

Received 4/ 2/91. Accepted 6/17/91.

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