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In Vivo Modulation of Macrophage Tumoricidal Activity by Oral Administration of the Liposome-encapsulated Macrophage Activator CGP 19835A¹

Departments of Cell Biology [S. T., C. D. B., M. R. W., I. J. F., J. J. K.] and Urology [A. C. v. E.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

The present study evaluated the in vivo biological activity of synthetic muramyl tripeptide, CGP 19835A, when encapsulated into phosphatidylcholine liposomes (POPC-19835A) and administered as an p.o. immunomodulator to BALB/c mice. Liposomes were rapidly absorbed in the intestine and reached the systemic circulation within 4 h. Alveolar macrophages harvested from the lungs of mice 24 h after a single p.o. feeding of POPC-19835A were tumoricidal toward syngeneic murine renal cell carcinoma target cells. Repeated daily feedings with POPC-19835A generated sustained activation of the alveolar macrophages. Activation of peritoneal macrophages to the tumoricidal state required at least three daily feedings of POPC-19835A. In vitro studies demonstrated the release of tumor necrosis factor and interleukin 6 by macrophages activated by POPC-19835A in the presence of -interferon. Interleukin 1 and nitric oxide were not induced in macrophages by this liposomal preparation. Daily administration of POPC-19835A after i.v. injection of renal cell carcinoma tumor in BALB/c mice inhibited the development of experimental lung metastasis and confirmed the potential role of long-term therapy with this new p.o. immunomodulator.

¹ Supported in part by NIH Core Grant CA-16672.

² Supported by a Research Fellowship Grant from the Canadian Kidney Foundation.

³ To whom requests for reprints should be addressed, at the Department of Cell Biology, Box 173, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.

Received 6/ 8/94. Accepted 9/13/94.

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