In situ activation of tumoricidal properties in rat alveolar macrophages and rejection of experimental lung metastases by intravenous injections of Nocardia rubra cell wall skeleton

Summary

The IV injection of squalene-treated cell wall skeleton of Nocardia rubra (N-CWS) into F344 rats rendered their alveolar macrophages (AM) tumoricidal. Maximum tumoricidal activity developed in AM by 24 h after the IV, but not IP or SC, injection of 300 μg N-CWS. Tumoricidal activity of AM was maintained for 48–72 h after one IV injection of N-CWS. Experimental lung metastases were produced in female F344 rats by the IV injection of viable syngeneic mammary adenocarcinoma cells. Treatments twice weekly with Hank's balanced salt solution, N-CWS placebo or N-CWS began 3, 7, or 10 days later and were continued for 3 or 4 weeks for a total of six or eight treatments. Practically all the rats (>90%) treated with N-CWS beginning on either day 3 or day 7 after tumor cell challenge survived until day 210, when the experiment was terminated. In contrast, 90% of the rats treated with balanced salt solution or N-CWS placebo died by day 70 of the experiment. Therapy with N-CWS preparation was not successful when the first injection was administered 10 days after tumor cell challenge, suggesting that this therapeutic regimen is effective only against minimal tumor burden. We conclude that in this animal tumor model, the IV injection of N-CWS preparations can render AM tumoricidal and aid in the eradication of pulmonary micrometastases.