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JNCI Journal of the National Cancer Institute 1988 80(14):1154-1159; doi:10.1093/jnci/80.14.1154
© 1988 by Oxford University Press
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Journal of the National Cancer Institute, Vol. 80, No. 14, 1154-1159, September 21, 1988
© 1988 Oxford University Press

Pharmacokinetics and Mechanism of Action of a Doxorubicin-Monoclonal Antibody 9.2.27 Conjugate Directed to a Human Melanoma Proteoglycan2,3

H. Ming Yang, Ralph A. Reisfeld4,5

4Department of Immunology, Scripps Clinic and Research Foundation 10666 North Torrey Pines Rd., La Jolla, CA 92037.

Doxorubicin (DXR) conjugated to a monoclonal antibody (MAb), 9.2.27, which recognizes a human melanoma-associated proteoglycan, effectively suppresses the growth of human melanoma xenografts and prolongs the life span of tumor-bearing athymic nude (nulnu) mice. We have investigated further the mechanism(s) of this in viva antitu-mor activity. Our results indicate that following iv injection, the DXR-MAb 9.2.27 conjugate is cleared from the circulation with typical Diphasic kinetics, similar to the clearance process of the unconjugated MAb 9.2.27. In contrast, less than 10% of injected dose per milliliter of blood is found in the circulation at any given time after ip injection. Toxicity studies further indicate that DXR-MAb 9.2.27 conjugate is less toxic in vivo than the freely administered DXR, which is known to cause considerable cardiotoxic effects. Direct autoradiography demonstrates that the DXR-MAb 9.2.27 conjugate binds specifically to the tissue sections derived from a human melanoma xenograft of a nude mouse. A critical evaluation is given of the relevance of these findings and their impact on the design of future strategies for the immunochemotherapy of malignant melanoma. [J Natl Cancer Inst 1988;80:l154–1159]


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