Kan N, Hori T, Ohgaki K, Inamoto T, Kodama H, Tobe T
Gan To Kagaku Ryoho. 1986 Apr;13(4 Pt 2):1298-306.
We have developed an adoptive immunotherapy (AIT) system using syngeneic tumor-bearer-spleen cells cultured with interleukin-2 (IL-2) and soluble tumor extract. The therapeutic effect of the AIT was significantly augmented by in vivo local preadministration of a streptococcal preparation, OK-432. The previous report demonstrated a mechanism in which OK-432 augments the effect of AIT. That is, OK-432 induces IL-2 in vivo and prolongs the in vivo life span of cultured, IL-2-dependent lymphocytes (CL). This paper describes another mechanism, that is, the synergism between CL and OK-432-induced host lymphocytes. Fresh spleen cells (FSC) obtained from mice in complete remission after chemotherapy (cyclophosphamide, 100 mg/kg) showed a clear synergistic anti-tumor effect on CL, when both were injected i.p. into MOPC104E-bearing BALB/c mice which had been inoculated i.p. with 1 X 10(5) tumor cells 5 days previously. The effect was greatest when the FSC: CL ratio was 4:1, whereas the administration of either FSC or CL alone had little effect. The effector population of CL that exhibited synergism on FSC was Lyt 2+, cytotoxic T cells. FSC and CL both needed a tumor-specific combination. In addition, OK-432-induced tumor-infiltrating, intraperitoneal lymphocytes had a similar synergistic effect on CL as assessed by the transplantability of intraperitoneal cells. Probably because of this mechanism, OK-432 showed a much higher augmenting effect on AIT using CL than in vivo administration of IL-2. This therapy system using OK-432 and CL is a proper model which, through combined use of different, correlated BRMs, may bring a great effect whereas the effect of single BRM is weak.
我们开发了一种过继性免疫疗法（AIT）系统，该系统使用与白细胞介素-2（IL-2）和可溶性肿瘤提取物一起培养的同基因荷瘤小鼠脾细胞。通过体内局部预先给予链球菌制剂OK-432，AIT的治疗效果得到显著增强。先前的报告证明了OK-432增强AIT效果的一种机制。也就是说，OK-432在体内诱导IL-2，并延长培养的IL-2依赖性淋巴细胞（CL）的体内寿命。本文描述了另一种机制，即CL与OK-432诱导的宿主淋巴细胞之间的协同作用。从化疗（环磷酰胺，100mg/kg）后完全缓解的小鼠获得的新鲜脾细胞（FSC），当二者经腹腔注射到5天前经腹腔接种1×10⁵个肿瘤细胞的荷MOPC104E的BALB/c小鼠体内时，对CL显示出明显的协同抗肿瘤作用。当FSC:CL比例为4:1时效果最佳，而单独给予FSC或CL几乎没有效果。对FSC表现出协同作用的CL效应细胞群体是Lyt 2⁺细胞毒性T细胞。FSC和CL都需要肿瘤特异性组合。此外，通过腹腔细胞的移植能力评估，OK-432诱导的肿瘤浸润性腹腔淋巴细胞对CL具有类似的协同作用。可能由于这种机制，OK-432对使用CL的AIT的增强作用比体内给予IL-2时高得多。这种使用OK-432和CL的治疗系统是一个合适的模型，通过联合使用不同的、相关的生物反应调节剂（BRM），可能会产生很大的效果，而单一BRM的效果较弱。
