Romani L, Fioretti M C, Bianchi R, Nardelli B, Bonmassar E
J Natl Cancer Inst. 1982 May;68(5):817-22.
Intracerebral tumor neutralization assay and adoptive immunotherapy with in vivo sensitized lymphocytes were done in immunodepressed mice challenged intracerebrally with L5178Y/DTIC lymphoma, a tumor subline antigenically altered by treatment with 5-(3,3-dimethyl-1-triazenyl)-1H-imidazole-4-carboxamide (DTIC) in vivo. Primary cytotoxic T-lymphocytes (CTL) were generated in vitro against L5178Y/DTIC cells with the use of splenocytes of histocompatible (BALB/cCr X DBA/2Cr)F1 donors. The extent of antitumor activity of CTL was evaluated by the measurement of tumor cell proliferation in the brain, as judged by the 125I-labeled 2'-deoxyuridine uptake values and by survival times of recipient mice. The results of the experiments showed: a) CTL were highly effective in inhibiting tumor growth when they were injected along with L5178Y/DTIC tumor cells in a Winn-type neutralization assay; b) the tumor inhibition mediated by CTL was specific, since no antilymphoma effects were detected when CTL sensitized against L5178Y/DTIC line were admixed with the parental L5178Y tumor or with other unrelated lymphoma cells; and c) local adoptive immunotherapy with CTL given on day 1, 3, or 5 after the intracerebral challenge with L5178Y/DTIC lymphoma substantially impaired tumor cell proliferation and significantly increased survival times of recipient leukemic mice.
在免疫抑制小鼠中进行了脑内肿瘤中和试验以及用体内致敏淋巴细胞进行的过继免疫疗法，这些小鼠经脑内接种L5178Y/DTIC淋巴瘤细胞进行攻击，该肿瘤亚系在用5-(3,3-二甲基-1-三氮烯基)-1H-咪唑-4-甲酰胺（DTIC）进行体内治疗后抗原性发生改变。使用组织相容性（BALB/cCr×DBA/2Cr）F1供体的脾细胞在体外产生针对L5178Y/DTIC细胞的原发性细胞毒性T淋巴细胞（CTL）。通过测量脑中肿瘤细胞的增殖来评估CTL的抗肿瘤活性程度，这通过125I标记的2'-脱氧尿苷摄取值以及受体小鼠的存活时间来判断。实验结果表明：a）在Winn型中和试验中，当CTL与L5178Y/DTIC肿瘤细胞一起注射时，它们在抑制肿瘤生长方面非常有效；b）CTL介导的肿瘤抑制是特异性的，因为当针对L5178Y/DTIC系致敏的CTL与亲本L5178Y肿瘤或其他无关淋巴瘤细胞混合时，未检测到抗淋巴瘤作用；c）在脑内接种L5178Y/DTIC淋巴瘤后的第1、3或5天给予CTL进行局部过继免疫疗法，可显著损害肿瘤细胞增殖并显著延长受体白血病小鼠的存活时间。
