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Treatment of Experimental Lung Metastasis with Local Thoracic Irradiation Followed by Systemic Macrophage Activation with Liposomes Containing Muramyl Tripeptide¹

Departments of Cell Biology [I. S., I. J. F.] and Experimental Radiotherapy [L. M., N. H.], The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston, Houston, Texas 77030

The purpose of these studies was to determine whether the combination of a low-dose local thoracic irradiation (LTI) followed by systemic activation of macrophages with liposomes containing muramyl tripeptide phosphatidylethanolamine (MTP-PE) would significantly decrease established experimental fibrosarcoma lung metastases. Male C3Hf/Kam mice were given i.v. injections of 1 x 10⁵ fibrosarcoma cells. Five days later, groups of mice were treated with saline, with 8 Gy LTI, or with liposomes containing MTP-PE or first with 8 Gy LTI and followed by multiple i.v. injections of liposomes containing MTP-PE. Most of the mice in the groups treated with liposomes died by day 42 of the experiment. In contrast, 60% of the mice treated with the combination of LTI and liposomes containing MTP-PE were alive by day 140 of the study. These mice were killed and were found to be free of tumors. Control studies demonstrated that liposomes administered i.v. to mice given LTI were trapped in the capillary bed of the lungs and activated the tumoricidal properties of lung macrophages.

We conclude that, in this combination, low-dose LTI, which can lead to both tumor cell death and inflammatory changes in the lung capillaries, could precede i.v. administration of liposomes containing MTP-PE. This combination of treatments can lead to destruction of tumor foci in the lung that cannot be achieved with either treatment alone.

¹ Supported by funds from the Stribling Endowed Chair for Cancer Research and Grant CA-062947 from the National Cancer Institute.

² To whom requests for reprints should be addressed, at Department of Cell Biology, Box 173, The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston, 6723 Bertner Avenue, Houston, TX 77030.

Received 2/10/86. Revised 5/29/86. Revised 7/10/86. Accepted 7/11/86.

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