脳腫瘍に対する免疫化学療法の基礎的研究 : 脳腫瘍実験モデルの開発およびPS-KとACNUによる免疫化学療法

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Syngeneic brain tumor cell lines were made from inbred Wistar King Aptekman/HKM (WKA/HKM) rats using ethylnitrosourea in our laboratory. Ethylnitrosourea was injected intravenously at a dose of 5O mg/kg into pregnant rats. Two kinds of tumor cell lines were established from offsprings after cell culture. One was mixed glioma which was named KEG-1, and the other was neurinoma which was named KEN-1. A immunochemotherapeutic study was attempted using KEG-1 cell lines. ACNU was injected intraperitoneally as chemotherapy. PS-K (protein-bound polysaccharide Kureha isolated from Basidiomycetes) was administered intraperitoneally as immunochemotherapy. Animals were divided into the following four groups. Group 1: Five × 10^4 viable cells of KEG-1 were inoculated to the right caudate nucleus on day 0. All rats receiving tumor cells died, with a mean survival time of 19.8 days. Group 2: ACNU was injected intraperitoneally at a dose of 20 mg/kg on day 3. Mean survival time was 32.6 days, showing a 64 percertt increase. Group 3: PS-K was injected intraperitoneally at a dose of 300 mg/kg, according to the time schedule. PS-K alone did not affect the mean survival time. Group 4: Five different timings of the combination of chemotherapy and immunotlterapy (group (a) to (e)) were investigated in this group. Group (a) animals received PS-K on days 0,1 and 2 before ACNU. Mean survival time was 32.6 days showing no increase compared to ACNU alone. Group (b) animals received PS-K on days 0,1,2,3,4 and 5 before and after ACNU. Mean survival time was 39.3 days, showing a 97.8% increase compared to controls. Group (c) animals received PS-K on days 0,1,2,6,7 and 8 before and after ACNU. Mean survival time was 37.2 days, showing an 87.8% increase. Group (d) animals received PS-K on days 3,4 and 5 after ACNU. Mean survival time was 37.3 days, showing an 88.4% increase. Group (e) animals received PS-K on days 6,7 and 8 after ACNU. Mean survival time was 38.0 days, showing a 91.9% increase. A marked effect was obtained when PS-K was injected before and after ACNU or after ACNU. When PS-K was injected before ACNU the mean survival time did not show any increase compared with that for ACNU alone. It appears that PS-K enganced the rat's immunity which was suppressed by ACNU. The immunity of the rats was not enhanced when PS-K was administered before ACNU since the biological activity of PS-K might be short lasting. It is suggested that therapeutic effects are not always augmented if immunotherapy is combined with chemotherapy at random, but it depends on the timing of the combination.
日本脳神経外科学会の論文
1980-10-15

脳腫瘍に対する免疫化学療法の基礎的研究 : 脳腫瘍実験モデルの開発およびPS-KとACNUによる免疫化学療法

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