{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:07:52Z","timestamp":1790165272846,"version":"4.1.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>\n                    Natural killer group 2 family of receptor A (NKG2A) and its ligand human leukocyte antigen-E (HLA-E) are increasingly recognised as an important immune checkpoint restraining lymphocyte populations involved in cancer immunity. Recent clinical studies investigating dual NKG2A\/programmed death ligand 1 (PD-L1) blockade versus anti-PD-L1 monotherapy suggest that the combination may be beneficial in immunotherapy-responsive disease settings. To date, clinical safety and efficacy results are only available for a single NKG2A-blocking monoclonal antibody (mAb). Here, we report on the generation and preclinical characterization of a novel NKG2A-blocking agent. The fully human Fc-attenuated immunoglobulin G1 mAb S095029, selected via functional antibody repertoire screening, was tested against benchmark clinical-stage antibodies in\n                    <jats:italic>in vitro<\/jats:italic>\n                    binding and functional NKG2A\/HLA-E blockade assays. S095029 bound human NKG2A with a low nanomolar-range affinity and efficiently reversed the inhibitory effects of NKG2A\/HLA-E interaction. As a single agent, S095029 enhanced the activation, cytotoxicity, and cytokine secretion of natural killer (NK) and \u03b3\u03b4 T cells. S095029 improved NK cell antibody-dependent cellular cytotoxicity and other effector functions triggered by Fc-competent mAbs.\n                    <jats:italic>In vivo<\/jats:italic>\n                    investigations in syngeneic mouse models showed that S095029 inhibited tumour growth by harnessing the anti-tumour activity of both NK and CD8+ T cells. Overall, our results support the clinical development of S095029 in immuno-oncology-responsive tumour settings with adequate HLA-E expression. Phase 1b\/2 dose escalation studies are currently underway to evaluate S095029 in combination with anti-PD-1 in non-small cell lung cancer and gastric cancer.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2026.1924010","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:55:27Z","timestamp":1790164527000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical characterization of S095029, a novel clinical-stage Fc-attenuated NKG2A-blocking antibody for cancer immunotherapy"],"prefix":"10.3389","volume":"16","author":[{"given":"Maria Carlsen","family":"Melander","sequence":"first","affiliation":[{"name":"Servier Symphogen A\/S","place":["Ballerup, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Uhlenbrock","sequence":"additional","affiliation":[{"name":"Servier Symphogen A\/S","place":["Ballerup, 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