The streptococcal preparation OK-432 specifically augments the susceptibility of human urinary bladder tumor cells to autologous peripheral blood lymphocytes

Abstract

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.