Tools for active specific immunotherapy with anti-idiotype antibodies in human renal cell carcinoma

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In apite of the increasing success in the management of urological malignancies, curative treatment of renal cell carcinoma (RCC) patients with metastatic disease still remains extremely difficult. Even with the multitude of therapeutic strategies, almost no improvement of the survival for these patients has been established in the last decade. It is well known that RCC is relatively resistant to conventional therapies and immunotherapy seems to be the most promising treatment for disseminated RCC.Obviously, the development of new therapeutic approach is necessary. We have developed internal image anti-idhiotype antibodies (Ab2) raised against MAbG250 which recognizes a large proportion of RCC,and also have shown that Ab2 vaccination resulted in the destruction of established tumor in mice. In the present study, we investigate therapeutic effects of MAbG250 immunotherapy in combination with cytokines (exp.1) and internal image Ab2 induced antisera (Ab3-82)(exp.2) in mice with RCC xenog … More rafts. Method : exp.1) Nu-nu BALB/c mice with approximately 20mm NUR2 human RCC xenografts were divided into 10 groups, i.e., gr.1 : control.gr.2 : IL-2, gr.3 : rm-IFN,gr.4 : MCSF,gr.5 : MAbG250, gr.6 : IL-2/MAbG250, gr. 7 : rm-IFN/MAbG250, gr.8 : MCSF/MAbG250, gr.9 : IL-2/IFN,gr.10 : IL-2/rm-IFN/MAbG250. Mice were treated with peri-tumor injection of 200 U/g mouse cytokines 5 days a week for 6 weeks. exp.2) Nu/nu mice with NUR2 xenografts were divided into 4 groups and treated with the following schedule for 6 weeks ; gr.1 : NMS (control)(0.2ml, i.p.3/week), gr.2 : MAbG250/IL-2/rm-IFN,gr.3 : Ab3-82 (0.2ml, i.p.3/week), gr.4 : Ab3-82+MCSF.Results : (exp.1) Treatment of NUR2 with IFN,IL-2, MAbG250, MCSF or IL-2/MAbG250 resulted in significant tumor growth inhibition (p<0.05) as compared to control group. In the remaining 3 groups, i.e., IL-2/IFN,IFN/MAbG250, IL-2/IFN/MAbG250, the tumor growth inhibition was greater than in the previous groups. (exp.2) Treatment of NUR2 RCC xenografts with IL-2/IFN/MAbG250, Ab3 based immunotherapy resulted in significant tumor growth inhibition compared to control group (gr.2,3 : p<0.01, gr.4 : p<0.0001). These findings suggest that Ab2 vaccination might be useful for specific immunotherapy in RCC patients. Less