| Project/Area Number |
58480278
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
General surgery
|
|---|
| Research Institution | Okayama University |
|---|
Principal Investigator |
ORITA Kunzo Okayama University Medical School, First Department of Surgery Professor, 医学部, 教授 (20033053)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TANAKA Noriaki Okayama University Medical School, First Department of Surgery Instructor, 医学部附属病院, 助手 (10127566)
SAKAGAMI Kennichi Okayama University Medical School, First Department of Surgery Assistant Profess, 医学部附属病院, 講師 (40124789)
|
|---|
| Project Period (FY) |
1983 – 1984
|
| Project Status |
Completed (Fiscal Year 1984)
|
| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1984: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1983: ¥2,800,000 (Direct Cost: ¥2,800,000)
|
|---|
| Keywords | LAK cell / interleukin 2 / neuraminidase / IL-2 slow delivery system / metastatic liver cancer / indomethacin |
|---|
| Research Abstract |
Large dose of interleukin 2(IL-2) and lymphokine activated killer(LAK) cells resulted in tumor regression in patients with certain advanced metastatic cancers, including renal cell carcinoma and melanoma. However, the therapeutic effects were limited to a minority of patients, and considerable toxicity accompanied the therapy. Further enhancement of the therapeutic effects of LAK cells requires studies on the following two problems, a) improvement of the accessibility of LAK cells to tumor tissues, and enhancement of the anti-tumor cytotoxicity of LAK cells.
In the clinical study, intraarterial injection of LAK cells was effective for the liver tumor. In order to obtain the same level of effects by infusion of LAK cells into the peripheral vein, the trap rate of LAK cells by the liver in needed to be elevated.
Neuraminidase treatment of LAK cells enhanced the accumulation of LAK cells in the liver, and resulted in a greater reduction of liver metastasis in the murine experimental model.
In order to circumbent of the severe toxicity of systemic administration of IL-2, we have developed a new biodegradable IL-2 slow delivery system, IL-2 minipellet (IL-2mp). The local administration of the IL-2mp around the target sites could produce significant antitumor activity in murin solid tumors. The local administration of the IL-2mp in the spleen was also effective in reducing the number of hepatic metastatic nodules and in prolonging the survival time of mice. The antitumor effects of IL-2mp were considered to be caused by generation of LAK cells in vivo, and their accumulation into the tumor site.
Prostaglandins are one of the main cause of suppression of natural killer activity in cancer bearing hosts. The combined administration of indomethacin and IL-2 could suppress the tumor growth and prolong the survival of tumor inoculated mice.
Above results are presenting several approachs for improvement of LAK therapy.
|
