Marta Michalska1, Susanne Schultze-Seemann1, Irina Kuckuck1, Philipp Wolf2. 1. Department of Urology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 2. Department of Urology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany philipp.wolf@uniklinik-freiburg.de.
Abstract
BACKGROUND: We generated humanized/de-immunized immunotoxins targeting the prostate-specific membrane antigen (PSMA) and tested their cytotoxic activity against prostate cancer cells in vitro. MATERIALS AND METHODS: The humanized/de-immunized version of our murine anti-PSMA single-chain antibody fragment (scFv) D7, termed hD7-1(VL-VH), was ligated to the 40-kDa toxin domain of Pseudomonas aeruginosa exotoxin A (PE40), and to the deimmunized 24-kDa toxin domains PE24 or PE24mut. The immunotoxins designated as hD7-1(VL-VH)-PE40, hD7-1(VL-VH)-PE24 and hD7-1(VL-VH)-PE24mut were bacterially expressed and purified by affinity chromatography. Binding and cytotoxicity were examined by flow cytometry and viability assay, respectively. RESULTS: All immunotoxins revealed strong binding to prostate cancer cells expressing PSMA and specific cytotoxicity, with half-maximal inhibitory concentration values in the picomolar range. CONCLUSION: We successfully created powerful anti-PSMA immunotoxins with reduced immunogenicity for further clinical development and application against advanced prostate cancer. Copyright
BACKGROUND: We generated humanized/de-immunized immunotoxins targeting the prostate-specific membrane antigen (PSMA) and tested their cytotoxic activity against prostate cancer cells in vitro. MATERIALS AND METHODS: The humanized/de-immunized version of our murine anti-PSMA single-chain antibody fragment (scFv) D7, termed hD7-1(VL-VH), was ligated to the 40-kDa toxin domain of Pseudomonas aeruginosa exotoxin A (PE40), and to the deimmunized 24-kDa toxin domains PE24 or PE24mut. The immunotoxins designated as hD7-1(VL-VH)-PE40, hD7-1(VL-VH)-PE24 and hD7-1(VL-VH)-PE24mut were bacterially expressed and purified by affinity chromatography. Binding and cytotoxicity were examined by flow cytometry and viability assay, respectively. RESULTS: All immunotoxins revealed strong binding to prostate cancer cells expressing PSMA and specific cytotoxicity, with half-maximal inhibitory concentration values in the picomolar range. CONCLUSION: We successfully created powerful anti-PSMA immunotoxins with reduced immunogenicity for further clinical development and application against advanced prostate cancer. Copyright
Authors: Jamal Alzubi; Viviane Dettmer-Monaco; Johannes Kuehle; Niko Thorausch; Maximilian Seidl; Sanaz Taromi; Wolfgang Schamel; Robert Zeiser; Hinrich Abken; Toni Cathomen; Philipp Wolf Journal: Mol Ther Oncolytics Date: 2020-06-24 Impact factor: 7.200
Authors: Corine Kruiswijk; Guilhem Richard; Merijn L M Salverda; Pooja Hindocha; William D Martin; Anne S De Groot; Elly Van Riet Journal: Hum Vaccin Immunother Date: 2020-01-17 Impact factor: 3.452