Hattori T, Niimoto M, Toge T, Hamamoto S, Seto Y, Kameda A, Tomoda S
Nihon Geka Gakkai Zasshi. 1984 Sep;85(9):1157-61.
As for the non-specific cancer immunotherapy concerned, the effect is limited and local use of immunopotentiators which could collect effector cells around tumor tissues might be the best way of cancer immunotherapy. Intratumoral or intraperitoneal administration of large-dose of OK-432 (100 KE) has been investigated since many years with favorable results. Side effects were minimum with a few days continuing slight fever elevation. From the immunohistological examinations using monoclonal antibodies, participation of killer T cells and NK cells was confirmed after intratumoral administration of large-dose OK-432. On the other hand, after intraperitoneal administration of OK-432, neutrophil leucocytes appeared at first on the 2nd to 4th day and they were followed by lymphocytes on the 4th to 5th day and finally appeared lot of macrophages on the 6th and later days. From the results of in vitro and in vivo experiments, these macrophages seemed to play the leading role in the cytostatic activities after intraperitoneal OK-432 administration. As for the fear of introducing suppressor cells after large-dose OK-432 administration, detailed studies on suppressor activities before and after operation for gastric cancer patients revealed no particular increase of suppressor cell activities after intratumoral and intraperitoneal administration of 100 KE OK-432 as compared with curative resection cases with no OK-432 administration.
至于非特异性癌症免疫疗法，其效果有限，在肿瘤组织周围聚集效应细胞的免疫增强剂局部应用可能是癌症免疫疗法的最佳方式。多年来一直研究大剂量（100KE）OK-432瘤内或腹腔内给药，效果良好。副作用最小，仅有几天持续低热。使用单克隆抗体进行免疫组织学检查显示，大剂量OK-432瘤内给药后，杀伤性T细胞和NK细胞参与其中。另一方面，腹腔内给予OK-432后，中性粒细胞在第2至4天首先出现，随后淋巴细胞在第4至5天出现，最后在第6天及以后出现大量巨噬细胞。从体外和体内实验结果来看，这些巨噬细胞似乎在腹腔内给予OK-432后的细胞抑制活性中起主导作用。至于担心大剂量OK-432给药后会引入抑制细胞，对胃癌患者手术前后抑制活性的详细研究表明，与未给予OK-432的根治性切除病例相比，瘤内和腹腔内给予100KE OK-432后抑制细胞活性没有特别增加。
