| Budget Amount *help |
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1988: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1987: ¥5,500,000 (Direct Cost: ¥5,500,000)
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| Research Abstract |
In order to examine the utility of interleukin 2 (IL 2) to renal cancer as an immunotherapeutic agent, we used the method of a 4-hour ^<51>chromium-release cytotoxicity assay and showed that peripheral blood lymphocytes (PBLs) stimulated with IL 2 were capable of lysing autologous cultured tumor cells. This finding demonstrated the applicability of adoptive immunotherapy with lymphokine-activated killer (LSK) cells in RCC patients. In the present study, we carried out adoptive immunotherapy with autologous LAK cells in conjunction with systemic administration of IL 2 in patients with advanced RCC. Moreover, in order to investigate the possibility of selection of appropriate candidates for this immunotherapy on the basis of the results of a ^<51>chromium-release cytotoxicity assay employing autologous tumor cells as the target, we looked for a correlation between in vitro autologous tumor cell lysis by LAK cells and the clinical response to the therapy.
Eleven men and 3 women with metast
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atic rcc were entered in this study. They were aged between 37 and 72 years and had undergone nephrectomy for histologically proven RCC. A large number of lymphocytes (PBLs) were separated from lymphocyte-rich fraction obtained from leukaphereses by density centrifugation on ficoll-hypaque. The cells were suspended in 1000 or 2000 ml of RPMI 1640 containing 2 units/ml of IL 3, 50 ug/ml of gentamicin and 5% heat-inactivated human AD serum. After cultivation for 3-4 days, the IL 2-stimulated PBLs (LAK cells) were infused to the patients. In addition, 1000 units of IL 2 were infused once or twice a day. Of 14 patients, a partial response was observed in 3. As toxic symptoms, headache and shaking chills occurred immediately after each infusion of LAK cells. The toxic symptoms of IL 2 probably consisted of fever, edema and eosinophilia. The ^<51>chromum-release cytotoxicity assay employing autologous tumor cells as the target was performed in 6 of the 14 patients. Autologous tumor lysis in the 3 patients showing a partial response was 30.0%, 5.9% and 52.0%. On the other hand, the lung metastases did not respond to the therapy in spite of high autologous tumor cell lysis of more than 90%. Thus, no significant correlation was found between the in vitro assay and the clinical response.
In conclusion, although a complete response could not be obtained, it can be said that this immunotherapy may be effective against RCC, particularly lung metastases, since a partial response was achieved in 3 of 14 patients. However, it should be taken into consideration that this immunotherapeutic approach may risk increasing the frequency of brain metastases. Less
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