Corynebacterium parvum (C. parvum) or stabilized poly I: C complex (poly ICLC) was administered to C57BL/6 mice with malignant gliomas induced by 20-methylcholanthrene.
The results were as follows. 1) When C. parvum was administered intracerebrally, growth of the brain tumor was significantly inhibited compared with intraperitoneal administration. Inhibition of tumor growth was obtained in proportion to the dose of C. parvum. Natural cytotoxic (NC) activity of brain mononuclear cells against malignant glioma cells was most enhanced when C. parvum was administered intracerebrally and that of peritoneal exudate cells was most enhanced when it was administered intraperitoneally in a 15 hour ⁵¹Cr release assay. Enhanced NC activity of brain mononuclear cells was found to reach a peak 5 days after intracerebral administration, and to depend on the administered dose. 2) When poly ICLC was administered intracerebrally, tumor growth was more inhibited than when it was administered intraperitoneally. Four administrations of poly ICLC at 4-day intervals showed significant inhibition of tumor growth compared with single administration. Enhanced NC activity of brain mononuclear cells against malignant glioma cells was found to reach a peak 1 day after intracerebral administration of poly I:C, and to depend on the frequency of intracerebral administration of poly ICLC. 3) Enhanced NC cells in the brain after administration of C. parvum and poly ICLC were observed mainly in the adherent cell fraction. 4) Tumor cell growth was inhibited when tumor cells were co-cultured with 250 μg/ml of C. parvum, but poly ICLC had no influence on tumor cell growth. 5) Interferon was not induced after intracerebral administration of C. parvum. High titers of interferon were observed after single intracerebral administration of poly ICLC, but much lower titers of interferon were observed after plural administration at 4-day intervals.
From these results, it was suggested that local administration of C. parvum or poly ICLC is effective in inhibiting the growth of brain tumors, that natural cytotoxicity of brain mononuclear cells is enhanced by intracerebral administration of C. parvum or poly ICLC with little interaction of interferon, and that there is a possibility of direct cytotoxic effects of C. parvum.