担脳腫瘍ラットを用いた養子免疫療法の研究

STUDY ON ADOPTIVE IMMUNOTHERAPY FOR THE EXPERIMENTAL BRAIN TUMOR

　抄録　脳腫瘍に対する養子免疫療法の可能性をラット脳腫瘍モデルを用いて検討すると共に，血清IL−2inhibitor （INH）についても検討を加えた。移植後7日目の担脳腫瘍ラットにLAK細胞と免疫獲得ラットの脾細胞（imm．　spc）を各々，静注および局注することにより，各群の生存率を対照群との間で比較した。その結果，生存率はLAK細胞投与群で有意に上昇していたがimm．　spc投与群では効果は認められなかった（LAK細胞静注群；25.1±2.9日，P＜0.01，局注群；23.8±4.2日，P＜0.05）。組織所見では，腫瘍内の壊死巣の出現頻度，面積ともにLAK細胞投与群で大であった。Microautoradiographyを用いて行った静注LAK細胞の臓器内分布は，静注後早期には肺，次いで肝，脾臓に集積する傾向にあり，脾臓では特にwhite pulpに認められた。又，脳腫瘍組織には，22時間後の検討では10個程度の細胞が瀰漫性に分布していた（40倍拡大）。IL−2 INH活性は担脳腫瘍ラットで上昇していたがCYの投与により著明に抑制された。以上より，LAK細胞のadoptive transferは脳腫瘍に対する有効な治療手段の一つとなり得ると考えられた。同時に，免疫療法の効果を一層高めるためにもIL−2 INHの性状を十分明らかにする必要があると思われる。

Adoptive immunotherapy for the experimental murine brain tumor has been investigated using LAK cells generated in vitro from normal spleen cells with IL-2 and immune spleen cells from Fischer rats immunized against syngenic gliosarcoma, T₉.

IL-2 inhibitor (s) activity in serum was alsostudied.

LAK cells and immune spleen cells were adop-tively transferred to the rats intravenously or in-tratumorally on the 7 th day after the inoculation of T₉ into the right basal ganglia. Then the sur-vival rate and necrotic foci were compared be-tween the groups treated with those cells and the control. The survival rate of the groups treated with LAK cells was significantly higher than that of the control (administrated intravenously ; P< 0.01, administrated intratumorally ; P<0.05). But the treatment with immune spleen cells was not effective. The incidence and area of necrotic foci in the tumors treated with LAK cells were greater than those of the others.

Microautoradiography was also performed using ³H-TdR labeled LAK cells, which were administ-rated intravenously to the model. It was revealed that LAK cells accumulated in lung shortly after the administration, then in liver and spleen, espe-cially in the white pulp.

IL-2 inhibitor activity of the sera from the tumor-bearers was greater than that of normal rats, while it was depressed markedly by cyclophospha-mide (60 mg/kg i. p.).

In conclusion, the adoptive transfer of LAK cells can be one of the effective and attractive treat-ments of the brain tumor. In order to make im-munotherapy more effective it should be necessary to clarify the nature of IL-2 inhibitor (s).