Natural Killer Cells in Patients with Renal Cell Cancer

Hofmann, R.; Lehmer, A.; Reidel, G.; Schütz, W.; Böttger, I.

doi:10.1159/000281093

Cited by 7 publications

References 9 publications

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Cytotoxic In vitro function in patients with metastatic renal cell carcinoma before and after alpha-2b-interferon therapy effects of activation with recombinant interleukin-2

Feruglio¹,

Zambello²,

Trentin³

et al. 1992

Cancer

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In this study the characteristics of the cytotoxic function in a series of patients with metastatic renal cell carcinoma (RCC) were analyzed and the possibility of modulating this capacity in vitro with the use of biologic response modifiers (BRM) such as alpha‐interferon (α‐IFN) and recombinant interleukin‐2 (rIL‐2) was verified, with the ultimate goal of providing a rationale for a therapeutic approach to this disease with these molecules. Peripheral blood mononuclear cells (PBMC) of patients with advanced RCC were tested for natural killer (NK) and lym‐phokine‐activated killer (LAK) activity both before and after α‐IFN therapy. In addition, surface markers of un‐stimulated and stimulated cells were analyzed and in vitro assays were performed to determine the proliferative capacity in response to the stimulus with rIL‐2. During an evaluation before treatment, defective NK activity was observed that could be corrected by incubating the cells with rIL‐2. In these subjects, LAK cells could be consistently generated after PBMC were activated with this cytokine in vitro. No changes in NK and LAK activity were found after α‐IFN therapy. In contrast, treatment with α‐IFN affected the proliferative response of PBMC to rIL‐2, and a significant decrease in this in vitro capacity was observed during follow‐up. The ability to restore NK activity and obtain an adequate LAK cytotoxicity from the PBMC of patients with RCC supports a therapeutic approach with BRM. However, the fact that this type of treatment affects the proliferative response of PBMC to rIL‐2 must be considered when clinical trials are designed for patients with RCC.

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Cytotoxic In vitro function in patients with metastatic renal cell carcinoma before and after alpha-2b-interferon therapy effects of activation with recombinant interleukin-2

Feruglio¹,

Zambello²,

Trentin³

et al. 1992

Cancer

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Daily alternating administration of high-dose alpha-2b-interferon and interleukin-2 bolus infusion in metastatic renal cell cancer. A phase II study

Bergmann

Fenchel

Weidmann

et al. 1993

Cancer

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Background. Both interleukin‐2 (IL‐2) and alpha‐interferon (α‐IFN) have some efficacy in renal cell cancer (RCC) as single agents. Additionally, there is some evidence for additive or synergistic antitumoral activity of IL‐2 and α‐IFN in vitro and possibly in vivo. Based on these data, the authors initiated a Phase II trial with a combination of recombinant IL‐2 (rIL‐2) and recombinant α‐IFN (α‐rIFN) in advanced RCC. Methods. Thirty‐six assessable patients with metastatic RCC were entered in this Phase II trial using a daily alternating schedule of α‐rIFN and rIL‐2. Over a period of 14 days, the patients received daily alternating treatment with 10 × 106 IU/m2 of recombinant alpha‐2b‐interferon subcutaneously and 18 × 106 IU/m2 of rIL‐2 as a 1‐hour intravenous infusion. This treatment schedule was repeated every sixth week up to a maximum of four cycles. After the second cycle, patients were examined for response. Patients with stable disease or better received two additional cycles of therapy. Patients with progressive disease were available for other strategies. Results. Thirty‐six patients entered the trial and were assessable for toxic effects. Thirty of 36 patients completed at least two cycles and were assessable for response. Nine patients achieved an objective response: 2 had complete responses (CR) and 7 had partial responses (PR). Three patients had a minor response. No effect was observed in patients with local relapse or bone metastases. A relapse‐free survival length of 6 months or longer was seen in both patients with CR (12, 23+ months) and in four of seven patients with PR (6, 7, 12, 12 months). The toxicity was moderate and included fever and nausea in most patients, and hypotension, fatigue, skin rash, and arthralgia in a minority of the patients. No Grade 4 and only occasionally Grade 3 toxicity was observed. Fluid retention was negligible. The monitoring of immunologic parameters showed a significant rebound lymphocytosis including cytotoxic (CD56+) cells; in responders the peak of lymphocytosis occurred up to 1 week later than in nonresponders. Peripheral lymphocytes obtained after therapy showed only a slight increase of natural killer cell and lymphokine‐activated killer cell activity. During therapy, there was a great release of secondary cytokines as tumor necrosis factor‐alpha, γ‐interferon, and interleukin‐6, with a peak level 2–4 hours after rIL‐2 infusion. Conclusions. In conclusion, daily alternating administration of α‐rIFN and rIL‐2 is effective in RCC with less toxicity, and the response rate is comparable to those of other immunotherapeutic schedules, including adoptive immunotherapy and combinations of high‐dose IL‐2 and α‐IFN.

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Immunotherapy of metastatic renal cancer

1988

Seminars in Surgical Oncology

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Various reports in the literature suggested active specific immunotherapy to be highly efficient in metastatic renal cell cancer (RCC). Thirty five patients with tumor stage III or IV, according to Robson, were treated with autologous or homologous cell vaccine after radical nephrectomy had been performed. In stage III tumors immunotherapy was administered as prophylaxis or after an interval, when metastases occurred. Clinical results during a 3-year follow-up period revealed no statistically significant differences in comparison to an age-matched control group. There was no advantage in employing autologous instead of homologous therapy. Three-year survival rate in stage IV tumors with autologous vaccination was 11% vs. 6% in tumors with homologous therapy. Two complete and two partial tumor remissions occurred.

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Natural Killer Cells in Patients with Renal Cell Cancer

Cited by 7 publications

References 9 publications

Cytotoxic In vitro function in patients with metastatic renal cell carcinoma before and after alpha-2b-interferon therapy effects of activation with recombinant interleukin-2

Cytotoxic In vitro function in patients with metastatic renal cell carcinoma before and after alpha-2b-interferon therapy effects of activation with recombinant interleukin-2

Daily alternating administration of high-dose alpha-2b-interferon and interleukin-2 bolus infusion in metastatic renal cell cancer. A phase II study

Immunotherapy of metastatic renal cancer

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