Effective Induction of Human NK Cells with OK‐432 and Further Augmentation of Their Cytolytic Function by rIL‐2

Abstract

Low concentrations of exogenously added recombinant interleukin 2 (rIL-2) were able to augment OK-432-induced natural killer (NK) cell activity. This kind of augmenting effect depended on the dose of rIL-2 and manifested itself only in PBMC stimulated with OK-432 (OK-MC) followed by rIL-2; augmentation did not happen in the reverse order. The existence of CD16+ /CD25+ (IL-2 receptor positive; IL-2R+) and CD57-VCD25+ double positive cells which possess NK cell surface markers in OK-MC markedly increased in a long-term culture (12 days). A strong positive correlation was observed between the IL-2-dependent augmentation of NK activity and the quantitative changes in cell populations that possessed NK cell phenotypes. Treatment of the day-12-OK-MC with monoclonal anti-CD56 antibody plus complement could almost completely abrogate the augmented NK cytotoxicity. Furthermore, this augmenting effect was detectable within 4 hr after addition of rIL-2 at single cell level, suggesting that the effect did not require NK cell's DNA synthesis. Thus it was suggested that OK-432 could promote and upregulate the expression of IL-2 receptor (CD25) on CD56+ NK cell populations. Moreover, it was considered that the interaction of low concentration rIL-2 with IL-2 receptors on OK-432-activated NK cells could augment their lytic function.

Inhibition of Human Peripheral Blood Mononuclear Cell Proliferation byStreptococcus pyogenesCell Extract Is Associated with Arginine Deiminase Activity

“…OK-432 is known to activate natural killer cells, T cells, and macrophages in vitro, and animals treated with OK-432 intraperitoneally develop antitumor cytotoxic macrophages (6). OK-432 induces proliferative responses of human PBMC, and they are thought to acquire antitumor activity which includes both cell-and cytokine-mediated mechanisms (20,40). Since OK-432 is a lyophilized preparation of the Su strain of S. pyogenes, it would be expected to contain SAGP and inhibit rather than induce proliferative responses of human PBMC.…”

Angiosarcoma of the scalp treated with OK‐432 and rIL‐2

“…It is assumed that these OK‐432 effects are induced by the elevation of multiple cytokines, including IL‐1, IL‐2, IL‐6, IL‐8, IL‐12, TNF, 8–11 and the activation of NK cells and LAK cells 12,13 …”

OK‐432 Therapy for Recalcitrant Warts

“…This drug is a well-known anti-tumor immunotherapeutic agent inJapan. OK-432 induces multiple cytokines, including IL-1, IL-2, IL-6, IL-8, TNF, and interferon (6)(7)(8) and also activates macrophages, cytotoxic T cells, and NK cells (9)(10)(11). Therefore, OK-432 could be expected to be effective for not only malignant tumors, but also viral diseases.…”