Antitumor activity of Corynebacterium parvum administered into the pleural cavity of mice

Summary

We investigated the efficacy of intrapleurally (IPl) injected 0.25 mg Corynebacterium parvum (CP) against pulmonary tumor deposits of four syngeneic murine tumors, C3Hf/Bu or CBA fibrosarcoma (FSa) or mammary carcinoma (MCa), and compared its efficacy with that of intravenous (IV) CP. A mode of action of CP given by IPl administration was also studied. When given to mice prior to the IV inoculation of tumor cells, IPl and IV CP reduced the number of metastases of C3Hf/Bu-FSa and CBA-MCa equally well. Intrapleural injection of CP within a week after tumor cell inoculation was more effective against metastases in the lung than IV CP. A combination of IPl and IV administration of CP was more effective in the therapy of lung metastases of CBA-FSa and CBA-MCa than either single treatment alone. Intrapleural and IV injections of CP augmented concomitant immunity to artificially produced lung metastases of C3Hf/Bu-FSa. Intrapleural CP was less effective than IV CP in inducing complete regression of the SC growing C3Hf/Bu-FSa.

In contrast to IV CP, IPl CP did not markedly influence the spleen weight and cellularity. It was also less effective in increasing the liver weight. However, CP by either route of injection led to a significant increase in the lung weight. CP injected IPl, but not IV, caused a significant increase in the number of nucleated cells in the pleural cavity of mice. More than 90% of these cells were macrophages, and they were found to be cytotoxic for in vitro cultures of CBA-MCa cells. Activated macrophages also mediated in vivo antitumor resistance, as shown by the abolition of this resistance by treatment of the mice with carrageenan.