Inhalation therapy using a streptococcal preparation (OK-432) against bronchioloalveolar carcinoma of the lung.

In order to inhibit the occurrence of airborne metastasis of bronchioloalveolar cell carcinoma (BAC), we tried to activate alveolar macrophages by the inhalation of aerosolized OK-432, which is a heat and penicillin-treated lyophilized preparation of the Su strain of Streptococcus pyogenes.Alveolar macrophages were obtained from resected specimens of lung cancer patients and cultured for 24 h in the presence of various concentrations of OK-432 (0.001-1 KE/ml). The cytotoxic activity against a lung cancer cell line was augmented in a dose dependent manner and reached a plateau level at 0.1 KE/ml of OK-432. Furthermore, the alveolar macrophages produced various cytokines, i.e., IL-1, TNF-alpha, and IL-6 after 72 h cultivation with 0.1 KE/ml of OK-432. Based on the in vitro experiments, six patients with intrapulmonary metastatic BAC were therefore treated by the inhalation of aerosolized OK-432. All 6 patients inhaled aerosolized OK-432 (0.1 KE/ml) twice a day for 5 days. The inhalation therapy regimen was repeated either weekly or monthly unless the tumor markedly progressed. No adverse events were observed in any patients. Either an augmentation of antitumor cytotoxicity or TNF-alpha production by the alveolar macrophages was observed in the two of three patients examined.OK-432 inhalation therapy was found to be safe and thus warrants further investigation to determine its clinical effectiveness for BAC.