Use of fibrinogen to enhance the antitumor effect of OK-432. A new approach to immunotherapy for colorectal carcinoma.
OK-432 (5 KE), an immunomodulatory agent prepared from an attenuated strain of Streptococcus pyogenes, was dissolved in 1 ml of aprotinin (1000 KIE) and mixed with 80 mg of fibrinogen containing Factor XIII. A single intratumoral injection of the mixture was performed preoperatively under endoscopy in 20 patients with colorectal carcinoma. Postoperative histopathologic examinations revealed the formation of fibrin fibers at the site of injection and marked infiltration of inflammatory cells into the tumor stroma on the day after injection; the formation of granulomas containing many giant cells after 4 to 7 days; and extensive regression of tumor tissue after 14 days. This study suggests that the high concentration of exogenous fibrinogen gelatinized enough to trap OK-432 in tumor stroma and that OK-432 induced granulomatous hypersensitivity to degenerate tumor stroma, thereby causing regression of the tumors.
Monden
T
T
Second Department of Surgery, Osaka University Medical School, Japan.
Morimoto
H
H
Shimano
T
T
Yagyu
T
T
Murotani
M
M
Nagaoka
H
H
Kawasaki
Y
Y
Kobayashi
T
T
Mori
T
T
D000230:Adenocarcinoma / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D007611:Aprotinin / Q000008:administration & dosage; D004338:Drug Combinations; D004357:Drug Synergism; D005176:Factor XIII / Q000008:administration & dosage; D005340:Fibrinogen / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007267:Injections; D010844:Picibanil / Q000008:administration & dosage / Q000627:therapeutic use*; D012004:Rectal Neoplasms / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D012811:Sigmoid Neoplasms / Q000473:pathology / Q000601:surgery / Q000628:therapy*
D004338:Drug Combinations; D010844:Picibanil; D005340:Fibrinogen; D005176:Factor XIII; D007611:Aprotinin