The Impact of a New Interleukin-2-Based Immunotherapy Candidate on Urothelial Cells to Support Use for Intravesical Drug Delivery

Abstract

(1) Background: The intravesical instillation of interleukin-2 (IL-2) has been shown to be very well tolerated and promising in patients with bladder malignancies. This study aims to confirm the use of a new IL-2 containing immunotherapy candidate as safe for intravesical application. IL-2, produced in mammalian cells, is glycosylated, because of its unique solubility and stability optimized for intravesical use. (2) Materials and Methods: Urothelial cells and fibroblasts were generated out of porcine bladder and cultured until they reached second passage. Afterwards, they were cultivated in renal epithelial medium (REM) and Dulbecco’s modified Eagles medium (DMEM) with the IL-2 candidate (IMS-Research) and three more types of human interleukin-2 immunotherapy products (IMS-Pure, Natural IL-2, Aldesleukin) in four different concentrations (100, 250, 500, 1000 IU/mL). Cell proliferation was analyzed by water soluble tetrazolium (WST) proliferation assay after 0, 3, and 6 days for single cell culture and co-culture. (3) Results: Proliferation assays showed that all IL-2 products induced very similar cultivation results and none of the IL-2 variants had a negative impact on the proliferation of urothelial cells and fibroblast in either concentration. (4) Conclusion: Human recombinant glycosylated IL-2 as well as human non-glycosylated IL-2 have no negative influence on the tissue cell proliferation of porcine urothelial cells and fibroblasts in vitro and represent a promising and innovative potential intravesical therapy candidate for patients in high need.

Keywords

• interleukin-2
• urothelial cells
• intravesical
• immunotherapy
• bladder cancer