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

(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...

Full description

Bibliographic Details
Main Authors: Lisa Schmitz, Belinda Berdien, Edith Huland, Petra Dase, Karin Beutel, Margit Fisch, Oliver Engel
Format: Article
Language:English
Published: MDPI AG 2020-10-01
Series:Life
Subjects:
Online Access:https://www.mdpi.com/2075-1729/10/10/231
_version_ 1797551771800829952
author Lisa Schmitz
Belinda Berdien
Edith Huland
Petra Dase
Karin Beutel
Margit Fisch
Oliver Engel
author_facet Lisa Schmitz
Belinda Berdien
Edith Huland
Petra Dase
Karin Beutel
Margit Fisch
Oliver Engel
author_sort Lisa Schmitz
collection DOAJ
description (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.
first_indexed 2024-03-10T15:50:43Z
format Article
id doaj.art-6bf7f1afe5984a5baaf8dca63b636ac3
institution Directory Open Access Journal
issn 2075-1729
language English
last_indexed 2024-03-10T15:50:43Z
publishDate 2020-10-01
publisher MDPI AG
record_format Article
series Life
spelling doaj.art-6bf7f1afe5984a5baaf8dca63b636ac32023-11-20T16:05:38ZengMDPI AGLife2075-17292020-10-01101023110.3390/life10100231The Impact of a New Interleukin-2-Based Immunotherapy Candidate on Urothelial Cells to Support Use for Intravesical Drug DeliveryLisa Schmitz0Belinda Berdien1Edith Huland2Petra Dase3Karin Beutel4Margit Fisch5Oliver Engel6Department of Urology, University Medical Center Hamburg-Eppendorf (UKE), 20251 Hamburg, GermanyImmunservice GmbH, 20251 Hamburg, GermanyImmunservice GmbH, 20251 Hamburg, GermanyDepartment of Urology, University Medical Center Hamburg-Eppendorf (UKE), 20251 Hamburg, GermanyDepartment of Urology, University Medical Center Hamburg-Eppendorf (UKE), 20251 Hamburg, GermanyDepartment of Urology, University Medical Center Hamburg-Eppendorf (UKE), 20251 Hamburg, GermanyDepartment of Urology, University Medical Center Hamburg-Eppendorf (UKE), 20251 Hamburg, Germany(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.https://www.mdpi.com/2075-1729/10/10/231interleukin-2urothelial cellsintravesicalimmunotherapybladder cancer
spellingShingle Lisa Schmitz
Belinda Berdien
Edith Huland
Petra Dase
Karin Beutel
Margit Fisch
Oliver Engel
The Impact of a New Interleukin-2-Based Immunotherapy Candidate on Urothelial Cells to Support Use for Intravesical Drug Delivery
Life
interleukin-2
urothelial cells
intravesical
immunotherapy
bladder cancer
title The Impact of a New Interleukin-2-Based Immunotherapy Candidate on Urothelial Cells to Support Use for Intravesical Drug Delivery
title_full The Impact of a New Interleukin-2-Based Immunotherapy Candidate on Urothelial Cells to Support Use for Intravesical Drug Delivery
title_fullStr The Impact of a New Interleukin-2-Based Immunotherapy Candidate on Urothelial Cells to Support Use for Intravesical Drug Delivery
title_full_unstemmed The Impact of a New Interleukin-2-Based Immunotherapy Candidate on Urothelial Cells to Support Use for Intravesical Drug Delivery
title_short The Impact of a New Interleukin-2-Based Immunotherapy Candidate on Urothelial Cells to Support Use for Intravesical Drug Delivery
title_sort impact of a new interleukin 2 based immunotherapy candidate on urothelial cells to support use for intravesical drug delivery
topic interleukin-2
urothelial cells
intravesical
immunotherapy
bladder cancer
url https://www.mdpi.com/2075-1729/10/10/231
work_keys_str_mv AT lisaschmitz theimpactofanewinterleukin2basedimmunotherapycandidateonurothelialcellstosupportuseforintravesicaldrugdelivery
AT belindaberdien theimpactofanewinterleukin2basedimmunotherapycandidateonurothelialcellstosupportuseforintravesicaldrugdelivery
AT edithhuland theimpactofanewinterleukin2basedimmunotherapycandidateonurothelialcellstosupportuseforintravesicaldrugdelivery
AT petradase theimpactofanewinterleukin2basedimmunotherapycandidateonurothelialcellstosupportuseforintravesicaldrugdelivery
AT karinbeutel theimpactofanewinterleukin2basedimmunotherapycandidateonurothelialcellstosupportuseforintravesicaldrugdelivery
AT margitfisch theimpactofanewinterleukin2basedimmunotherapycandidateonurothelialcellstosupportuseforintravesicaldrugdelivery
AT oliverengel theimpactofanewinterleukin2basedimmunotherapycandidateonurothelialcellstosupportuseforintravesicaldrugdelivery
AT lisaschmitz impactofanewinterleukin2basedimmunotherapycandidateonurothelialcellstosupportuseforintravesicaldrugdelivery
AT belindaberdien impactofanewinterleukin2basedimmunotherapycandidateonurothelialcellstosupportuseforintravesicaldrugdelivery
AT edithhuland impactofanewinterleukin2basedimmunotherapycandidateonurothelialcellstosupportuseforintravesicaldrugdelivery
AT petradase impactofanewinterleukin2basedimmunotherapycandidateonurothelialcellstosupportuseforintravesicaldrugdelivery
AT karinbeutel impactofanewinterleukin2basedimmunotherapycandidateonurothelialcellstosupportuseforintravesicaldrugdelivery
AT margitfisch impactofanewinterleukin2basedimmunotherapycandidateonurothelialcellstosupportuseforintravesicaldrugdelivery
AT oliverengel impactofanewinterleukin2basedimmunotherapycandidateonurothelialcellstosupportuseforintravesicaldrugdelivery