The effects of HDIL-2 in combination with pazopanib or sunitinib on PBMCs’ function and RCC cells’ apoptosis: Preliminary in vitro data.

Abstract

463 Background: Combination of certain immunotherapies with TKI’s has been used with success in the treatment of metastatic renal cell carcinoma (MRCC) patients. Here we evaluate the in vitro effects of HDIL-2 and pazopanib or sunitinib on the PBMCs’s function and RCC cell lines apoptosis. Methods: PBMCs isolated from healthy donors or RCC patients were treated with different HDIL-2/TKI combination and their proliferation was assessed with CFSE labelling assay. Furthermore, using CD107a degranulation or chromium release assays, the function of these treated cells was evaluated. The BRdU assay was used to examine the effects of these drugs combinations on the proliferation of different RCC cell lines. Results: While HDIL2/sunitinib combination did not inhibit the proliferation of various immune cells induced by HDIL-2 alone, combination of HDIL-2/pazopanib did, on the other hand, inhibit these cells proliferation. Interestingly, none of these combinations had a negative impact on the functional properties of these cells. Significant proportion of RCC cell lines treated with pazopanib underwent apoptosis, while the proportions of apoptotic cells post HDIL-2 or sunitinib treatment were not different from the background. Furthermore, the combination of HDIL-2/pazopanib did not inhibit the pazopanib induced RCC apoptosis. Conclusions: These preliminary data showed that combination of HDIL-2 and either pazopanib or sunitinib could recruit different anticancer mechanism that could enhance the treatment efficacy. Further assessment in this direction is warranted.