The anti-tumor effect of local immunotherapy using BCG and Picibanil, a Streptococcus pyogenes preparation, was evaluated in experimental and human malignant brain tumors.
BCG and Picibanil produced an identical inflammatory cell reaction in the C
3HHe mouse brain after intracerebral injection. BCG had no direct cytocidal effect on Rous sarcoma virus-induced malignant glioma cells of the mouse in vitro. A mixture of the mouse glioma cells and BCG was inoculated into the subcutaneous tissue and brain of the syngeneic mice. The development and growth of subcutaneous and brain tumors were inhibited remarkably by the addition of 100-1, 000 μg of BCG to 2×10
5 subcutaneously transplanted tumor cells, and by the addition of 50-500 μg of BCG to 1×10
4 intracerebrally transplanted tumor cells. Intratumoral injection of 5 mg of BCG showed a significant suppression of the growth of subcutaneous tumors which could not be obtained by the systemic administration of the same dose of BCG. The enhancement of tumor-specific immunity was obtained in this mouse-tumor system by the repeated immunization of a mixture of irradiated tumor cells and BCG.
Thirteen patients with malignant brain tumors, 12 anaplastic gliomas and one metastatic tumor, received repeated intratumoral injections of Picibanil through one to two intratumorally implanted tubes. All patients tolerated this therapy, and the morbidity rate was acceptable. Significant tumor regression was noted on CT scans in 6 of 11 patients for whom scanning was performed. Histologic examinations of the post-therapy specimens obtained from 9 patients revealed that inflammatory cell reactions were evoked in all of the tumors, although the extent of the inflammatory reactions varied from tumor to tumor and was mostly localized to an area surrounding the intratumoral tubes.
Combination therapy of local Picibanil injection and systemic administration of ACNU as maintenance immunochemotherapy was performed in another series of anaplastic glioma patients. Among the 10 patients who were followed for more than 2 years after treatment, 5 survived more than 2 years and 4 obtained long-term survivals of 71, 58, 44 and 43 months postoperatively.
In conclusion, local immunotherapy is worth employing as maintenance immunochemotherapy for anaplastic glioma patients.
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