髄芽腫患者に対する養子免疫療法

ADOPTIVE IMMUNOTHERAPY FOR PATIENTS WITH MEDULLOBLASTOMA BY LAK CELLS

　抄録　小児脳腫瘍の中で，最も発生頻度の高い腫瘍の一つである髄芽腫は，放射線に感受性が高く，腫瘍亜全摘ののち放射線療法を行うと，治療終了時に腫瘍の播種さえ生じていなければ，その5年生存率は60-80％と報告されている。しかしこの腫瘍は，他の神経膠芽腫と異なり脳脊髄腔内に播種しやすく，播種後の平均余命は1年未満であると報告されている。また発育期にある脳に50-60Gyという大量の放射線照射を行うため，就学などの社会復帰の程度はあまり良い結果を得ていない。そこで我々は，8例の小児髄芽腫患者に対し，肉親の末梢リンパ球より誘導したLAK細胞を用いて養子免疫療法を行い，3症例に有効な結果を得た。この養子免疫療法を行う前に，各症例毎に，患者と肉親のリンパ球を用いてmixed lymphocytereaction （MLR）を行い，コントロールと比べて重篤な免疫反応が生じないことを確かめて治療を行っている。副作用としては，治療時に生じる発熱以外主たる副作用を認めなかった。十分な免疫学的配慮の下にこの治療を行えば，手術，放射線・化学療法および養子免疫療法を重ねて行うことができ，更に，良い治療結果が得られる可能性が示唆された。

Medulloblastoma is one of the most popular ma-lignant brain tumors in children. It accounts for about 15% of all pediatric brain tumors. Radio-chemotherapy has prolonged the 5-year survival rate up to 60-85% for patients with medullobla-stoma. But the conventional therapy is not so effective to recurrent cases, especially with menin-geal dissemination, and generally fatal. There remains a big problem of the neurotoxicity to in-fants in a growth process under the whole-neuraxis irradiation and chemotherapy. Aiming to relieve the radiation and antitumor drugs, adoptive immu-notherapy is greatly expectant. We have had clinical trials of adoptive immunotherapy for 8 patients with medulloblastoma by lymphokine-activated killer (LAK) cells. They were from 2-9 years in age and had cerebrospinal fluid (CSF) dis-semination of the tumors. All patients underwent the whole-neuraxis irradiation and chemotherapy. After they had CSF dissemination, they were sub-mitted to an adoptive transfer of allogeneic LAK cells. LAK cells were induced from peripheral blood lymphocytes (PBL) of their relatives with human recombinant interleukin-2. 3-15 x 109 LAK cells were transferred intrathecally in 2-3 months. In 3 of 8 patients, neurological signs were improved and malignant cells had never been detected on CSF cytology after the adoptive immunotherapy. One among these 3 patients showed complete res-ponse in 20 months. Thus, this is an attractive treatment for patients with medulloblastoma, espe-cially with CSF dissemination, which cannot be cured by current therapeutic intervention.