Immunotherapy for malignant gliomas (author's transl)

Abstract

Recently the authors investigated the therapeutic effects of specific and non-specific immunotherapies used as adjuvant therapy to surgical resection of malignant gliomas followed by 60Co radiation therapy, and obtained some results suggesting the effectiveness of these therapies. For the purpose of non-specific activation of cell-mediated immunity, the authors administered an immunopotentiator, OK-432, intramuscularly to 13 patients with intracerebral gliomas over a long period. Cell-mediated immunity of these patients before and during immunotherapy was investigated by means of various tests including delayed cutaneous hypersensitivity reactions against PPD and PHA, and lymphocyte and T-cell counts in the peripheral blood. The following methods of specific immunotherapy were used in nine patients with malignant gliomas. Resection of the tumor was first carried out and a link between the space left after the tumor resection and the lateral ventricle of the lesioned side was produced provided that no malfunction would result from this procedure. An appropriate amount of autologous lymphocytes separated from the peripheral blood of the patient was repeatedly infused through a catheter inserted into the space left after the tumor resection, either before or after 60Co irradiation therapy. When a recurrence of the glioma was found, resection of the recurrent tumor was again performed and a histopathological investigation of the tissue was carried out. The average survival period of the nine patients who received the afore-mentioned specific immunotherapy was statistically compared by the Wilcoxson test with that of twelve control patients with glioblastomas who underwent only tumor resection followed by radiation therapy. Cell-mediated immunity of patients with gliomas tended to be reinforced by non-specific immunotherapy. Successive CT scannings of the head performed on patients who received specific immunotherapy revealed that the space left after the tumor resection appeared to be a low density area poorly demarcated from the surrounding brain tissue. With the lapse of time, the low density area became clearly demarcated and remained as it was, even though a tumor recurred in the surrounding brain. Histological observation revealed that the brain tissue adjacent to a space filled with CSF was covered with a thick fibrous membrane with abundant newly developed capillaries or sinusoid-like vessels. Recurrent tumors tended to be located beneath the membrane. Numerous foci of necrosis were actually observed in association with abundant lymphocyte infiltration, suggesting that there is a possibility of immunologically competent cells wandering into the tumor tissue through the newly developed vessels. The average survival periods of patients with and without specific immunotherapy were 23 months and 10.3 months respectively. There was a statistically significant difference in the survival periods between the two groups (P<0.05).