1995 Fiscal Year Final Research Report Summary
Immunochemotherapy for advanced ovarian cancer
| Project/Area Number |
05454459
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Cancer Institute, Japanese Foundation for Cancer Research |
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Principal Investigator |
HASUMI Katsuhiko Chief, Cancer Institute, 部長 (70134608)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Yoshio Cancer Institute, 研究員 (60260072)
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| Project Period (FY) |
1993 – 1995
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| Keywords | Ovarian cancer / Immunotherapy / Priming / Antigenicity / OK 432 |
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| Research Abstract |
A) Animal experimental model :
We used OK 432 as a BRM for treating peritonitis carcinomatosa in animal experimental model in the consideration of clinical application. C3H/HeN mice were S.C.primed or not with 0.1 KE of OK 432 on day 1 and subsequently inoculated with viable tumor cells(10^5/mice)on day 10. Mice developed carcinomatous ascites around on day 15. Both control and OK-primed mice received IP-OK 432(10 KE)on day 17. Of 10 mice primed with OK 432,9 showed complete disappearance of malignant ascites, whereas only 1 mouse showed regression in ascites of 10 control mice. In vitro immune analyzes revealed OK-primed mice exhibited significantly enhanced IL-2 production and potent anti-tumor CTL through T-T cell interaction. Thus, significance of priming in induction of augmented in vivo immunity was demonstrated.
B) Human application :
Based on the results of experimental model, clinical trial was conducted on ovarian cancer patients with peritonitis carcinomatosa. One-hundred and fifteen patients were randomised to receive SC injection with 0.2 KE OK 432 on day 1 and 8 or not. Both OK-primed and not-primed patients received 10 KE of OK 432. Fifty-nine patients primed with OK 432 demonstrated 29 CRs and 18 PRs with overall response rate being 79.7%. On the other hand, 56 patients not primed with OK 432 showed 11 CRs and 16 PRs with the response rate being 48.2%, which was significantly(p < 0.01)worse compared with that of OK-primed patients.
In vitro immune analyzes revealed IL-1beta, IL-2, IL-6, INF-gamma, LAK activity, and NK activity in ascites were significantly enhanced in OK-primed patients.
C)Conclusion :
Intraperitoneal injection with OK 432 in the presence of priming with low-dose of OK 432 could deliver a significant treatment effecy on carcinomatous ascites. Theoretically this modality can be applicable to any type of carcinomatous ascites.
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