Mizutani Y, Nio Y, Yoshida O
Department of Urology, Faculty of Medicine, Kyoto University, Japan.
Cancer. 1992 Jun 15;69(12):2999-3007. doi: 10.1002/1097-0142(19920615)69:12<2999::aid-cncr2820691223>3.0.co;2-a.
The streptococcal preparation OK-432 was tested for its ability to enhance the susceptibility of fresh urinary bladder tumor (UBT) cells to autologous peripheral blood lymphocytes (PBL) in patients with UBT. PBL treated with OK-432 at 0.1 Klinishe Einheit (KE)/ml for 18 hours killed the human T24-lined UBT cells and freshly separated autologous UBT cells more efficiently than untreated PBL. Treatment of K562 erythroleukemia cells with OK-432 at 0.1 KE/ml for 18 hours had no effect on their susceptibility to lysis by fresh PBL. In contrast, treatment of T24 and fresh autologous UBT cells with OK-432 resulted in an enhancement of their susceptibility to PBL. The susceptibility of autologous UBT cells to both large granular lymphocytes (LGL) and T-lymphocytes was also enhanced by treatment of tumor cells with OK-432. Binding of PBL to T24 and fresh autologous UBT cells was also augmented by treatment of the tumor cells with OK-432. The frequency of binding of OK-432 to fresh UBT cells was positively correlated with the increased target sensitivity to autologous PBL. The inhibition of RNA synthesis in fresh UBT cells by OK-432 was also associated with the elevated susceptibility to autologous PBL. These results indicate that OK-432 activates the autologous tumor killing system through stimulation of effector cells and elevation of target susceptibility to effector cells in patients with UBT, and suggest that the OK-432-augmented target sensitivity to PBL may be oriented specifically to UBT cells and local immunotherapy with OK-432 may be remarkably beneficial in the treatment of UBT.
对链球菌制剂OK-432进行了测试，以检验其增强膀胱尿路上皮癌（UBT）患者新鲜膀胱肿瘤细胞对自体外周血淋巴细胞（PBL）敏感性的能力。用0.1克林氏单位（KE）/毫升的OK-432处理PBL 18小时后，其杀伤人类T24系UBT细胞和新鲜分离的自体UBT细胞的效率比未处理的PBL更高。用0.1 KE/毫升的OK-432处理K562红白血病细胞18小时，对其被新鲜PBL裂解的敏感性没有影响。相反，用OK-432处理T24细胞和新鲜自体UBT细胞会增强它们对PBL的敏感性。用OK-432处理肿瘤细胞也增强了自体UBT细胞对大颗粒淋巴细胞（LGL）和T淋巴细胞的敏感性。用OK-432处理肿瘤细胞也增加了PBL与T24细胞和新鲜自体UBT细胞的结合。OK-432与新鲜UBT细胞的结合频率与靶细胞对自体PBL敏感性的增加呈正相关。OK-432对新鲜UBT细胞RNA合成的抑制也与对自体PBL敏感性的提高有关。这些结果表明，OK-432通过刺激效应细胞和提高靶细胞对效应细胞的敏感性来激活自体肿瘤杀伤系统，提示OK-432增强的靶细胞对PBL的敏感性可能特异性地针对UBT细胞，并且用OK-432进行局部免疫治疗可能对UBT的治疗非常有益。
