1991 Fiscal Year Final Research Report Summary
Synergistic anti-tumor activity between IL-2-cultured lymphocytes and fresh lymphocytes
| Project/Area Number |
02807112
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | Kyoto University |
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Principal Investigator |
KAN Norimichi Kyoto University Faculty of Medicine Research Assister, 医学部, 助手 (50186160)
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| Project Period (FY) |
1990 – 1991
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| Keywords | Interleukin-2 / Killer T cells / Adoptie immund therapy / Immuno chemo therapy / OK-432 / Cyclophosphamide / CD8+cells / Synergistic antitumor activity |
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| Research Abstract |
Fresh lymphocytes(FL)in cancer patients were cultured for 13 days with T-cell growth factor, interleukin-2 and sonicated tumor extract. We examined lysis of autologous tumor cells(12-h 5ICr release test)by cultured lymphocytes(CL)when the same number of CL and FL were added to the assay system(E/T=40 : 1).
1. A randomized protocol study in Stage II or Ill breast cancer patients shows suppressive activitv of FL in 3/9 of no treatment group, but no suppressive activity in immuno-chemotherapy(OK-432 and cyclophosphamide)group(enhanced activity in 3/7).
2. In 18 patients with liver metastases from breast cancer, FL in 6/18 showed enhanced activity and in 7/18 suppressive activity in the lysis of autologous tumor cells of CL.
3. In flow cytometric analysis, CD8+CDllb+ cells and CD16+ cells significantly decreased after immuno-chemotherapy in both groups(Stage ll, or III breast cancer and liver metastases from breast cancer)
4. In vitro assays using autologous and allogerieic tumor fells, FL showed some specificity in enhanced and suppressive activity against the cytotoxicity of CL.
5. The main population of FL which influenced the cytotoxicity of CL W. 3. s plastic rionakihererit. And especially CD8-depleted FL enhanced the cytotoxicitv of CL.
6. In liver metastases from breast cancer, the survival after recurrence w as prolonged in enhanced group but survival after treatment was not significantly prolonged in enhanced group.
These results suggest that immuno-chemotherapy eliminates suppressive population in FL and may induce the synergistic activity between FL and CL against autologous tumor cells. To clarify the mechanism of AIT, we should pay attention to cellular interaction among autologous tumor cells, transferred cultured cells and host fresh cells induced by immuno-chemotherapy.
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