Search for immunobiological parameters predictive of clinical effects of OK-432 in patients with malignant ascites.
Although OK-432, a potent BRM, has been known to induce the remarkable improvement of clinical conditions in cancer patients through its strong effects on their immune capabilities, no specific immune parameters have been identified to best predict the clinical outcome after the OK-432 treatment. In an attempt to identify early parameters indicative of the clinical effects, we have administered 0.1 mg of OK-432 intraperitoneally to a total of 12 patients with malignant ascites and examined peritoneal fluid and peripheral blood obtained on 4 days before, 1, 3, and 7 days after the OK-432 injection using various immunobiological assays. Four weeks later, clinical improvements were evaluated by the disappearance of malignant cells from and/or substantial decrease in ascites. Four patients (responders) showed the improvements while 8 patients (nonresponders) showed no clinical evidence for improvement. In a few parameters among the many examined, significantly different patterns of changes were noted between responders and nonresponders. Thus, in nonresponder patients MO and T cell population returned to an initial low level after early increases (on days 1 and/or 3), while they remained increased day 1 through 7 in responders. In responder patients, the cytotoxicity of peritoneal mononuclear cells against K562 and Daudi cells were augmented on day 7, but not in nonresponder patients. The in vitro stimulation of the mononuclear cells with OK-432 enhanced the cytotoxic activity and induced the interferon (IFN) production in the responders but not in nonresponders. These parameters will be useful for the early prediction of the expected clinical effects of OK-432.
Kataoka
M
M
Department of BRM, Tokyo Institute for Immunopharmacology, Inc., Japan.
Hashimoto
S
S
Nanjo
M
M
Saito
M
M
Sugawara
Y
Y
Yoshida
T
T
Kamano
T
T
Urabe
M
M
Nishimura
K
K
Sakakibara
N
N
D000328:Adult; D000368:Aged; D001201:Ascites / Q000276:immunology / Q000473:pathology / Q000628:therapy; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007372:Interferons / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D010844:Picibanil / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D007155:Immunologic Factors; D007375:Interleukin-1; D007376:Interleukin-2; D009363:Neoplasm Proteins; C030193:immunosuppressive acidic protein; D010844:Picibanil; D007372:Interferons