Comparative effects of Corynebacterium parvum, Brucella abortus extract, Bacillus Calmette-Guérin, glucan, levamisole, and tilorone with or without cyclophosphamide on tumor growth, macrophage production, and macrophage cytotoxicity in a murine mammary tumor model

Abstract

In this laboratory, it has been repeatedly demonstrated (using a murine mammary tumor model) that the combination of cyclophosphamide (CY) and Corynebacterium parvum (CP) is more effective than either agent alone in the control of tumor growth. This paper presents information obtained in our model comparing findings on the effects of CP with a Brucella abortus extract (Bru-Pel; BP) and glucan (GL) on tumor growth. In addition, the influence of those agents as well as bacillus Calmette-Guérin, tilorone, and levamisole on bone marrow macrophage colony production and cytotoxicity is presented. None of the nonspecific stimulating agents (NSSAs) inhibited tumor growth when administered systemically without CY, confirming our previous contention that such immunotherapy alone is likely to be an ineffectual form of treatment. Whereas tumor regression was observed following intratumor CP, neither GL nor BP had such an effect. When used with CY, neither BP nor GL administered ip or intratumorally inhibited tumor growth as effectively as did CP and CY. Inhibition of the growth of a distant tumor as well as the treated tumor occurred following intratumor CP and CY but not following intratumor BP and CY. All of the microbial NSSAs increased macrophage colony production to varying degrees in both normal and tumor-bearing mice. In the latter mice, CP had the most prolonged effect. Levamisole and tilorone failed to increase colony production in normal mice while in tumor-bearing mice the effect was inversely proportional to the amount of agent administered. To some extent, the stimulation of colony production by the NSSAs paralled the degree of tumor inhibition observed when those agents were combined with CY. The cytotoxicity of cultured macrophages could not be related to tumor growth inhibition.