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Metastatic renal cell carcinoma (mRCC) is a difficult to treat malignancy and currently Sunitinib is a standard of care first-line therapy. A new metastasis during the treatment is considered a sign of drug failure and alternative therapeutic methods should be tried. Here, we report 2 cases of newly diagnosed isolated metastasis during Sunitinib treatment of mRCC patients. Our management plan included local palliative therapy to the lesion followed by recommencing of Sunitinib. This resulted in a good symptomatic relief locally as well as good overall control of the disease. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

CD4+CD25+ regulatory T (Treg) cells are present in increased numbers in patients with advanced cancer and CD25+ T cell depletion potentiates tumour immunity in animal models. The aim of this study was to assess the feasibility and safety of adoptive transfer of CD25+ depleted autologous T cells in patients with advanced renal cell carcinoma and to examine resulting changes in lymphocyte subsets. Six patients with advanced renal cell carcinoma underwent leukapheresis followed by conditioning chemotherapy with cyclophosphamide and fludarabine. The autologous leukapheresis product was depleted of CD25+ cells using CliniMACS® System then re-infused into the patient. Efficient CD25+ depletion from all leukapheresis products was achieved and 0.55–5.87 × 107/kg CD3+ cells were re-infused. Chemotherapy related haematological toxicity was observed, but blood counts recovered in all patients allowing discharge after a mean inpatient stay of 21 days. One patient subsequently developed a rapidly progressive neurological syndrome. A transient reduction in CD25+ subset was noted in the peripheral blood of 5 out of 6 patients with evidence of increased T cell responses to PHA in 4 out of 6 patients. One patient showed increased specific proliferative responses to the tumour associated antigen h5T4 coinciding with the nadir of Treg cells. Given the transient nature of the reduction in CD25+ subset and the observed toxicity there is a need to explore further strategies to improve the safety and efficacy of this approach. Nevertheless, the results provide proof of concept in potentiation of tumour antigen T cell responses when Treg cell levels are depleted. [ABSTRACT FROM AUTHOR]

Objective: Combination of immunotherapy with tyrosine kinase inhibitors (TKIs) has been used with some success for the treatment of metastatic renal cell carcinoma. Herein we evaluate the in vitro effect of high-dose interleukin-2 (HDIL-2) and pazopanib or sunitinib on the lymphocyte function and on induction of apoptosis in renal cell carcinoma (RCC) cell lines., Methods: Peripheral blood mononuclear cells (PBMCs) isolated from healthy donors or RCC patients were treated with different HDIL-2/TKI combinations. Effects of different combinations on proliferation and cytotoxic activity of PBMCs were evaluated, in addition to their effect on apoptosis of three different RCC cell lines., Results: While sunitinib did not inhibit the proliferation of various immune cells induced by HDIL-2, pazopanib appeared to inhibit the HDIL-2-induced proliferation of these cells. Interestingly, none of the HDIL-2/TKI combinations appeared to compromise the functional properties of these cells. Additionally, significant proportion of RCC cell lines treated with pazopanib alone underwent apoptosis, while the proportions of apoptotic cells post-HDIL-2 or sunitinib were not different from the background. Furthermore, the combination of HDIL-2/pazopanib did not inhibit the pazopanib-induced RCC apoptosis., Conclusion: The combination of HDIL-2 with either pazopanib or sunitinib exerts different anticancer mechanisms that could enhance the treatment efficacy.

Approximately 90% of renal cell tumors overexpress the tumor antigen 5T4. The attenuated strain of vaccinia virus, modified vaccinia Ankara, has been engineered to express 5T4 (TroVax). We conducted an open-label phase 1/2 trial in which TroVax was administered alongside interferon-alpha (IFNalpha) to 11 patients with metastatic renal cell carcinoma. Antigen-specific cellular and humoral responses were monitored throughout the study, and clinical responses were assessed by measuring the changes in tumor burden by computed tomography scan (Response Evaluation Criteria In Solid Tumors). The primary objective was to assess the safety, immunogenicity, and efficacy of TroVax when given alongside IFNalpha. Treatment with TroVax plus IFNalpha was well tolerated with no serious adverse events attributed to TroVax. All 11 patients mounted 5T4-specific antibody responses and 5 (45%) mounted cellular responses. No objective tumor responses were seen, but the overall median time to progression (TTP) of 9 months (range: 2.1 to 26+ mo) was longer than expected for IFNalpha alone. For the 10 clear cell patients the TTP ranged from 3.9 to 26+ months, with a median TTP of 10.4 months. The high frequency of 5T4-specific immune responses and prolonged median TTP for clear cell patients compared with that expected for IFNalpha alone is encouraging and warrants further investigation.