悪性神経膠腫におけるOK−432の腫瘍腔内直接投与による抗腫瘍効果—その基礎的及び臨床的効果について

Antitumor Effect of Direct Intra-Tumor Administration of OK-432 on Malignant Glioma:Basic and clinical observations

I．はじめに

　抗腫瘍溶連菌製剤OK−432を投与することにより，マウスの血清中^2）または腹水中^7）に腫瘍細胞に対してCytotoxicに作用するFactorが誘導されることは知られている．1986年吉永ら^9）は胸腔内にOK−432を投与された悪性胸膜炎患者の胸水がL−929細胞に対してCytotoxicityを示すことを報告している．また，田中ら4）は悪性脳腫瘍患者の腫瘍内に設置したOmmaya's tubeよりくり返しOK−432を投与することにより，抗腫瘍効果を認めたと報告している．今回，われわれは悪性グリオーマ患者の腫瘍腔内にOK−432を投与することによってCytotoxic Factorを誘導し得るか否か，またFactorの出現と臨床効果との関連性をみるために実験的及び臨床的検討を行った．その結果，若干の知見を得たので報告する．

Abstract

In this study, we tried to examine the efficacy of a cytotoxic factor which is induced by periodic, repeated local administration of OK-432 into the tumor cavity of malignant glioma patients.

OK-432 was administered intratumorally via a tube to 4 malignant glioma patients on Days 1, 3, 5, 7 and 12 in doses of 0.5 KE, 1 KE, 2 KE, 2 KE, and 3 KE, re-spectively. Cerebrospinal fluid (CSF) was collected several times during the 24-hour period beginning im-mediately after the administration on Day 12. The CSF was added to the culture medium of rat glioma cells (GA-1 and C-6) in order to observe the cytotoxic effect morphologically. The clinical efficacy in the patients was evaluated from the changes in tumor size observed by CT.

CSF collected from the tumor cavity of 3 patients was bloody. By adding this bloody CSF, a significant morphological cytotoxic effect was observed on both the GA-1 and C-6 glioma cells in culture. The level of cytotoxicity was higher with the bloody fluid collected at 4 to 24 hours after the final administration than with the bloody fluid collected immediately after the final administration. The cytotoxic effect of this fluid was stronger than that of rabbit TNF (tumor necrosis factor) serum induced with P. acnes and LPS.

In summary, the major findings of this study were (1) tumor cavity fluid collected 4 to 24 hours after the final OK-432 administration showed a remarkable cyto-toxic effect, (2) bloody fluid showed a clearer cytotoxic effect on cultured glioma cells, and tumor shrinkage was observed (by CT) in the patients who had bloody fluid in the tumor cavity, and (3) this fluid showed a stronger cytotoxic effect than TNF serum derived from rabbits.

Therefore, repeated local administration of OK-432 into a tumor can be expected to induce a strong en-dogenous cytotoxic factor.