Adoptive immunotherapy by pantropic killer cells recovered from OK-432-injected tumor sites in mice.
Adoptive immunotherapy by pantropic killer cells recovered from OK-432-injected tumor sites in mice.
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从注射 OK-432 的小鼠肿瘤部位回收的泛嗜杀伤细胞进行过继免疫治疗。
作者：
M. Saito;M. Nanjo;M. Kataoka;Y. Moriya;Y. Sugawara;Takeshi Yoshida;N. Ishida
先前建立了BAMC-1肿瘤小鼠恶性腹水模型，连续5次腹水完全治愈。注射OK-432。我们发现这些动物的腹膜单核细胞含有抗肿瘤效应细胞，可以在体外非特异性地破坏多种肿瘤细胞。它们暂时被称为泛嗜杀伤细胞（PKC）。本研究的主要目的是通过使用过继免疫治疗模型来显示 PKC 的体内抗肿瘤功效。皮下移植的 BAMC-1 肿瘤的生长5 天前，通过将 OK-432 注射到携带 BAMC-1 的供体小鼠中诱导的 5 x 10(6) 至 2 x 10(7) PKC 被动转移，显着抑制了 5 天前的免疫反应，而使用 OK-432 处理的同一供体的免疫脾细胞需要超过 1 x 10(8) 个免疫脾细胞才能达到类似的效果。此外，如果在过继移植前1小时对荷瘤受体进行180 mg/kg的环磷酰胺预处理，即使是5 x 10(6) PKCs也可以诱导5天前移植的肿瘤完全消退。该方案甚至可以在 12 天前移植的受者体内实现较大肿瘤（直径 9-10 毫米）的完全消退。正如预期的那样，PKC 不仅能够治愈携带 BAMC-1 的动物，还能够治愈携带 Meth-A 的小鼠。因此，作为过继性免疫疗法的效应细胞，OK-432 诱导的 PKC 似乎与通过用白细胞介素 2 培养肿瘤浸润淋巴细胞在体外扩增的淋巴因子激活的杀伤细胞一样有效，甚至更好。尽管对 PKC 表面标志物的研究并未明确区分它们与淋巴因子激活的杀伤细胞，但目前的研究结果被认为具有重要意义，表明有效的生物反应修饰剂（如 OK-432）可以诱导泛嗜性杀伤细胞，这些细胞在体内破坏各种肿瘤细胞方面极为有效。因此，OK-432疗法相对于淋巴因子激活杀伤细胞疗法的优势之一是，前者不需要后者所必需的繁琐且耗时的体外程序。
A murine malignant ascites model with BAMC-1 tumors was established previously, which was cured completely by five consecutive i.p. injections of OK-432. We have found that peritoneal mononuclear cells from these animals contained antitumor effector cells which could destroy nonspecifically a variety of tumor cells in vitro. They were tentatively called pantropic killer cells (PKCs). The present study was essentially designed to show the antitumor effectiveness of the PKCs in vivo by the use of an adoptive immunotherapy model. The growth of BAMC-1 tumors transplanted s.c. 5 days earlier was significantly suppressed by passive transfer of 5 x 10(6) to 2 x 10(7) PKCs induced by injection of OK-432 into BAMC-1 bearing donor mice, while more than 1 x 10(8) immune spleen cells from the same donors treated with OK-432 were required to achieve the similar effects. Furthermore, if the tumor-bearing recipients were pretreated with 180 mg/kg of cyclophosphamide 1 h before the adoptive transfer, even 5 x 10(6) PKCs could induce complete regression of the tumors transplanted 5 days earlier. This protocol made it possible even to achieve the complete regression of larger tumors (9-10 mm in diameter) in recipients transplanted 12 days earlier. The PKCs were, as expected, able to cure not only BAMC-1-bearing animals but also Meth-A-bearing mice. As effector cells for adoptive immunotherapy, therefore, the PKCs induced by OK-432 seem to be as effective as, if not better than, lymphokine-activated killer cells expanded in vitro by culturing tumor infiltrating lymphocytes with interleukin-2. Although the study on surface markers of PKCs did not unequivocally discriminate these from lymphokine-activated killer cells, the present findings are considered significant indicating that a potent biological response modifier such as OK-432 can induce pantropic killer cells which are extremely effective in destroying various tumor cells in vivo. One of the advantages of OK-432 therapy over lymphokine-activated killer cell therapy, therefore, is that the former does not require the tedious and time-consuming in vitro procedures which are essential for the latter.
小鼠骨髓移植后，淋巴细胞因子激活的杀伤细胞先于经典细胞毒性 T 淋巴细胞产生。
DOI：
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发表时间：
1985
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Merluzzi,VJ;Savage,DM;Smith,MD;Last-Barney,K;Mertelsmann,R;Moore,MA;Welte,K
通讯作者：
Welte,K