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Adriamycin-induced Modulation of Host Defenses in Tumor-bearing Mice¹

Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, New York 14263

Using the C57BL/6/EL4 tumor model, studies were carried out to demonstrate the feasibility of administering Adriamycin (ADM) in therapeutic doses and schedules such that the host antitumor defenses would not be suppressed and in some cases might be stimulated by treatment. ADM treatment caused prolongation of survival and, in general, either stimulated host cytolytic activities above untreated control levels or had no effect. These effects by ADM were observed with the ADM-sensitive parent EL4 line as well as with an ADM-resistant subline, indicating that the effects did not result entirely from direct antitumor activity. The cytolytic activities examined were those of cytolytic T-lymphocytes, lymphokine-activated killer cells, and splenic and peritoneal macrophages. All activities were assessed against the syngeneic EL4 target line. The information obtained in this investigation provides a rational basis for the future development of curative protocols with ADM plus biological response modifiers, which would depend on a functional immune system for optimum efficacy and would also exploit synergistic immunomodulating effects of the agents used in combination.

¹ Supported in part by USPHS Grants CA-24538, CA-16056, CA09072, and CA-15142 awarded by the National Cancer Institute, Department of Health and Human Services.

² To whom requests for reprints should be addressed.

³ Present address: Life Technologies, Inc., Grand Island, NY 14072.

Received 2/25/91. Accepted 4/17/92.

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