Profound Functional Suppression of Tumor-Infiltrating T-Cells in Ovarian Cancer Patients Can Be Reversed Using PD-1-Blocking Antibodies or DARPin® Proteins
Joint Authors
Rådestad, E.
Mattsson, J.
Uhlin, M.
Klynning, Charlotte
Schoutrop, Esther
Förster, Judith M.
Krieg, Jennifer
Mörtberg, Anette
Müller, Mischa R.
Herzog, Christel
Schiegg, Dieter
Villemagne, Denis
Fiedler, Ulrike
Snell, Dan
Kebble, Benjamin
Levitsky, Victor
Source
Journal of Immunology Research
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-08-04
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
PD-1/PD-L1 blockade has revolutionized the field of immunooncology.
Despite the relative success, the response rate to anti-PD-1 therapy requires further improvements.
Our aim was to explore the enhancement of T-cell function by using novel PD-1-blocking proteins and compare with clinically approved monoclonal antibodies (mAbs).
We isolated T-cells from the ascites and tumor of 17 patients with advanced epithelial ovarian cancer (EOC) and analyzed the effects using the mAbs nivolumab and pembrolizumab and two novel engineered ankyrin repeat proteins (DARPin® proteins).
PD-1 blockade with either mAb or DARPin® molecule significantly increased the release of IFN-γ, granzyme B, IL-2, and TNF-α, demonstrating successful reinvigoration.
The monovalent DARPin® protein was less effective compared to its bivalent equivalent, demonstrating that bivalency brings an additional benefit to PD-1 blockade.
Overall, we found a higher fold increase of lymphokine secretion in response to the PD-1 blockade by tumor-derived T-cells; however, the absolute amounts were significantly lower compared to the release from ascites-derived T-cells.
Our results demonstrate that PD-1 blockade can only partially reinvigorate functionally suppressed T-cells from EOC patients.
This warrants further investigation preferably in combination with other therapeutics.
The study provides an early pilot proof-of-concept for the potential use of DARPin® proteins as eligible alternative scaffold proteins to block PD-1.
American Psychological Association (APA)
Rådestad, E.& Klynning, Charlotte& Schoutrop, Esther& Förster, Judith M.& Krieg, Jennifer& Mörtberg, Anette…[et al.]. 2020. Profound Functional Suppression of Tumor-Infiltrating T-Cells in Ovarian Cancer Patients Can Be Reversed Using PD-1-Blocking Antibodies or DARPin® Proteins. Journal of Immunology Research،Vol. 2020, no. 2020, pp.1-12.
https://search.emarefa.net/detail/BIM-1187453
Modern Language Association (MLA)
Rådestad, E.…[et al.]. Profound Functional Suppression of Tumor-Infiltrating T-Cells in Ovarian Cancer Patients Can Be Reversed Using PD-1-Blocking Antibodies or DARPin® Proteins. Journal of Immunology Research No. 2020 (2020), pp.1-12.
https://search.emarefa.net/detail/BIM-1187453
American Medical Association (AMA)
Rådestad, E.& Klynning, Charlotte& Schoutrop, Esther& Förster, Judith M.& Krieg, Jennifer& Mörtberg, Anette…[et al.]. Profound Functional Suppression of Tumor-Infiltrating T-Cells in Ovarian Cancer Patients Can Be Reversed Using PD-1-Blocking Antibodies or DARPin® Proteins. Journal of Immunology Research. 2020. Vol. 2020, no. 2020, pp.1-12.
https://search.emarefa.net/detail/BIM-1187453
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1187453