ヌードマウス可移植性ヒト悪性グリオーマに対する免疫化学療法

IMMUNOCHEMOTHERAPY OF HUMAN GLIOMAS TRANSPLANTED INTO NUDE MICE

　抄録　ヌードマウス可移植性ヒト悪性グリオーマに対して免疫；化学療法の単独あるいは併用効果の有無，とくにインターフェロンの腫瘍内局所投与の効果の有無を調べた。手術時摘出した脳腫瘍株をヌードマウス（Balb C nu/nu）背部皮下に移植して継代能となった，乏突起膠腫と，膠芽腫株について実験を施行した。化学療法の有効性について，まずスクリーニングを施行両腫瘍に対してビンクリスチンが有効（⧺）であることが判明した。特に乏突起膠腫に，対してはビンクリスチンとアドリアマイシンが用量依存性に効果を示し，ビンクリスチンの1mg/kg 1回腹腔内投与は，0.2mg/kg/週，5同投与の効果と実験開始1カ月の時点でほぼ一致した。免疫療法剤としては，PSK，OK−432，組み換え型ヒト白血球インターフェロンを使用した。PSKは15mgを腹腔内；局注3回（dayO，1，2）とし，OK−432は1KE単位を1回（day O）；2回（day 0，1）腹腔内あるいは局所投与し，インターフェロンは100万単位を連日7日間腹腔内投与あるいは局注した。その結果，PSKを除き免疫療法剤は単独でも効果を示したが，特にインターフェロンは局注が腹腔内投与より効果を示した。また化学療法剤との併用効果は明らかである。

　In the first part of this paper, various chemotherapies were performed against oligodendrogliomas subcutaneously transplanted in to nude mice. Vincristine (VCR), adriamycin, and 1000 rads irradiation were effective against this tumors. Concerning these two drugs, dose response effect was observed. And the effect of 1 mg/kg injection of VCR roughly corresponded to that of five weekly injections of 0.2 mg/kg.

　In the second part of this experiment, single or combined effects cf VCR and immunotherapeutic agents including OK-432 (0K), PSK, and recombinant leucocytic interferon (IFN) were examined. Two glioma lines including oligodendrcglioma and glioblastoma were used. Following results were obtained from this experiment : I) Effect of OK and VCR against oligodendrogliomas were as follows : control <OK local injection (Local) <OK intraperitoneal injection (IP) ; VCR ; OK (IP × 2) <VCR OK (IP) <VCR: OK (IP ×2). Effects of OK ard VCR were expressed in orderof their effects against glioblastomas : control <VCR <OK (IP); OK (IP× 2); OK (Local) <VCR + OK (IP); VCR +0K (IP × 2). Effects of PSK and VCR against glioblastomas were as follows : control; PSK (Local) <VCR <VCR LPSK (Local) <VCR +PSK (IP). Effects of IFN and VCR against oligodendrogliomas were as follows : control ; IFN (IP) <VCR <IFN (Local) <VCR+IFN (IP) ; VCR +IFN (Local). Effects of IFN and VCR against glioblastomas were as follows : control <IFN (IP) <VCR ; IFN (Local); VCR+ IFN (IP).

　From these results, it can be concluded that : 1) There were no definite changes in morphologic and chemotherapeutic responsiveness in these two glioma lines after serial transplantations. 2) Immunotherapy alone (OK-432 ; IFN) was effective to reduce the growth of these tumor lines, especially local injection of IFN was potent. 3) There was a definite combined effect of VCR and immunotherapeutic agents.

　Finally, these glioma lines transplanted into nude mice are very important not only to select the most appropriate therapeutic regimens, but also to elucidate the mechanism of the effect of these agents.

　Further study including the variation of the immunological parcimeters will be required.