J.Jpn. Surg. Soc.. 92(1): 31-36, 1991

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Original article

INTRATUMORAL INJECTION OF OK-432 IN CONJUNCTION WITH FIBRINOGEN GREATLY
ENHANCES ANTITUMOR EFFECT ON COLORECTAL CARCINOMAS

We found that antitumor effect of OK-432, a lyophylized preparatlon of an attenuated strain of streptococcus pyogenes, on colorectal carcinoma was greatly augmented when it was injected intratumorally in conjunction with fibrinogen. Twenty cases of colorectal cancer received intratumoral injection of 5 KE of OK-432 mixed with 80mg of fibrinogen including factor-XIII and 1ml of aprotinin at the time of endoscopic examination. Changes in the shape of the tumors were observed endoscopically within a few days after injection, and in most cases,decrease in the height of tumor margin was noted.
Histopathological findings on surgically resected specimens revealed that the fine meshwork of fibrin was formed at the injected site soon after the injection, and a marked infiltration of infiammatory cells including neutrophils, plasma cells, macrophages, eosinophils and lymphocytes. Such granulomatous changes developed over 7 days after injection, and the degradation of tumors were observed, By 14 days after the injection, tumor tissues were largely replaced with granulomas, and shrinkage of tissues were observed.
These findings indicated that fibrinogen including factor-XIII and aprotinin has a potential ability to augment the immunoreaction induced by biological response modifiers, and intratumoral injection of OK-432 in conjunction with fibrinogen solution was superior to intratumoral injection of OK-432 alone as the local immunotherapy of colorectal cancer.

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