{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T09:46:52Z","timestamp":1782899212348,"version":"3.54.5"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T00:00:00Z","timestamp":1596499200000},"content-version":"vor","delay-in-days":216,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Immunology Research"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p>\n                    PD\u20101\/PD\u2010L1 blockade has revolutionized the field of immunooncology. Despite the relative success, the response rate to anti\u2010PD\u20101 therapy requires further improvements. Our aim was to explore the enhancement of T\u2010cell function by using novel PD\u20101\u2010blocking proteins and compare with clinically approved monoclonal antibodies (mAbs). We isolated T\u2010cells 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\u00ae proteins). PD\u20101 blockade with either mAb or DARPin\u00ae molecule significantly increased the release of IFN\u2010\n                    <jats:italic>\u03b3<\/jats:italic>\n                    , granzyme B, IL\u20102, and TNF\u2010\n                    <jats:italic>\u03b1<\/jats:italic>\n                    , demonstrating successful reinvigoration. The monovalent DARPin\n                    <jats:italic>\u00ae<\/jats:italic>\n                    protein was less effective compared to its bivalent equivalent, demonstrating that bivalency brings an additional benefit to PD\u20101 blockade. Overall, we found a higher fold increase of lymphokine secretion in response to the PD\u20101 blockade by tumor\u2010derived T\u2010cells; however, the absolute amounts were significantly lower compared to the release from ascites\u2010derived T\u2010cells. Our results demonstrate that PD\u20101 blockade can only partially reinvigorate functionally suppressed T\u2010cells from EOC patients. This warrants further investigation preferably in combination with other therapeutics. The study provides an early pilot proof\u2010of\u2010concept for the potential use of DARPin\n                    <jats:italic>\u00ae<\/jats:italic>\n                    proteins as eligible alternative scaffold proteins to block PD\u20101.\n                  <\/jats:p>","DOI":"10.1155\/2020\/7375947","type":"journal-article","created":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T19:31:39Z","timestamp":1596569499000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Profound Functional Suppression of Tumor\u2010Infiltrating T\u2010Cells in Ovarian Cancer Patients Can Be Reversed Using PD\u20101\u2010Blocking Antibodies or DARPin\u00ae 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