Intratumoral Injection Of OK-432 Research Articles

Evidence that eosinophil infiltration in the OK-432/fibrinogen-injected Meth-A tumor in mice is mediated by locally produced IL-5

It was previously demonstrated that a single injection of OK-432 (a penicillin-treated freeze-dried Streptococcus) mixed with fibrinogen into cancer tissues induces marked infiltration by eosinophils of the tumor stroma and leads to tumor necrosis. In the present study, we examined mechanisms regulating the local accumulation of eosinophils and the role of infiltrating eosinophils in tumor regression using the OK-432/fibrinogen injected Meth-A fibrosarcoma tumor. After injection of OK-432/fibrinogen into the tumor on the left flank of the BALB/c mice, eosinophil infiltration became obvious in the tumor stroma on day 3 following the accumulation of macrophages and neutrophils, was massive on day 5 and decreased by day 10. After the decrease in the infiltration of eosinophils, the tumor injected with OK-432/fibrinogen diminished markedly in size with ulceration as compared with control. Northern blot analysis revealed that expression of IL-5 mRNA in the tumor tissue was not detected on day 0, was significantly on day 3, reached the maximum on day 5, and thereafter decreased by day 10. Although intraperitoneal injection of rat anti-IL-5 monoclonal antibody in tumor bearing mice prior to OK-432 injection inhibited the infiltration of eosinophils, the antitumor effects of OK-432 persisted. In the blood, neither eosinophilia nor IL-5 activity was recognized during the course of the experiment. These results suggest that intratumoral injection of OK-432/fibrinogen induces local production of IL-5, which in turn recruits eosinophils into the tumor tissue, however, the infiltrating eosinophils do not play an important role in tumor regression.

大腸癌に対する術前ＯＫ‐４３２腫よう内投与の免疫学的意義に関する検討

大腸癌に対する術前ＯＫ‐４３２腫よう内投与の免疫学的意義に関する検討

Intratumoral injection of OK432 and lymphokine-activated killer activity in peripheral blood of patients with hepatocellular carcinoma

Lymphokine-activated killer (LAK) activity of peripheral blood mononuclear cells (PBMC) from 33 patients with hepatocellular carcinoma was significantly decreased compared with that of healthy volunteers. There was less LAK activity in PBMC from patients with larger tumours (5 cm or more in diameter) than in patients with smaller tumours (under 5 cm in diameter). In 8 out of 20 patients with larger tumours there was none or little LAK activity. Flow cytometry revealed that the percentage of Leu11b+ cells in PBMC was lower in patients than in normal volunteers, and was lowest in patients with larger tumours. 10 patients with hepatocellular carcinoma were treated with intratumoral injection of OK432. LAK activity was enhanced after treatment in 7 cases, and the percentage of Leu11b+ cells was increased. Enhancement of LAK activity in response to OK432 was more significant in patients with smaller rather than larger tumours. Of the 7 high LAK responders, 4 showed 50–100% tumour regression at 6–9 weeks after injection.

ＯＫ‐４３２の局所投与が反対側頚部転移病巣の著明な腫よう縮小効果を示した上顎歯肉癌症例

A metastasis was recognized in the contralateral lymph node after radiation therapy and surgical operation including ipsilateral radical neck disection and primary tumor excision for gingival squamous cell carcinoma (T3N2bM0). Intramuscular injection of pepleomycin was initially carried out with no tumor regression. In addition to the above chemotherapy, therefore, we treated this patient with intratumoral injection of OK-432, resulting in marked reduction in size of the metastatic lesion. It is thus suggested that intratumoral administration of OK-432 with or without chemotherapy maybe effective for such a recurrent case of oral cancer.