Antitumor activities of OK-432-stimulated peripheral blood mononuclear cells (PBMC) were examined. Killer activity against natural killer (NK) cell-sensitive K562 as well as lymphokine activated killer (LAK) cell-sensitive Daudi and PC3 target cells were detected among PBMC cultured with a low dose (0.0125-0.05 KE/ml) of OK-432. Kinetic analysis of killer activity showed that it reached a plateau level by 48 h of culture. Various freshly isolated tumor cells from oral cancer patients were also lysed by both the autologous and allogeneic OK-432-stimulated PBMC (OK-MC), suggesting that the specificity of the killer was not restricted by HLA and was thus non-specific. Fluorescence activated cell sortor (FACS) analyses showed that CD57+/CD25+ and CD16+/CD25+ cells were increased in PBMC after 48-h stimulation with OK-432. The killer activity was further augmented by the addition of rIL-2 at the time of killer assay.
Tumor growth inhibitory factor (TGIF) activity, which we previously reported, was found in the culture supernatant (CSN) of OK-MC from various cancer patients. The titer of TGIF from these patients was high enough, 16-64 × of the reciprocal dilution of the CSN, which was almost equivalent to the activity from normal healthy controls.
These results suggest that two kinds of antitumor activities were induced in the OK-432-stimulated PBMC in vitro, the one being cell-mediated and the other lymphokine-mediated (TGIF). OK-MC is thus supposed to be effective for adoptive immunotherapy (AIT) in oral cancer patients.