{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T07:16:03Z","timestamp":1788419763036,"version":"build-2803163510"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Cell-based immunotherapies of PBMC-derive Natural killer (NK) cells have demonstrated substantial potential for the treatment of hematologic malignancies. However, its application is limited due to the complex and inefficient gene modification\n                      <jats:italic>in vitro<\/jats:italic>\n                      and the insufficient therapeutic efficacy against solid tumors\n                      <jats:italic>in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Herein, a novel bispecific fusion protein 16Fc21(Anti-CD16A-FC-IL21) with capacity of modulate NK cell function is designed and constructed to try to breakthrough these limitations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In this work, we demonstrated that 16Fc21 has excellent ability to induce the functional activation of PBMC-derived NK cells and improve the therapeutic efficacy of NK cell immunotherapy for solid tumors\n                      <jats:italic>in vivo<\/jats:italic>\n                      . Additionally, we developed a novel combination therapy by combining adoptive transfer of NK cell with 16Fc21. We pre-arming 16Fc21 onto the surface of NK cells and successfully developed a non-genetically modified 16Fc21 armedNK (16Fc21 armed-eNK) technology platform.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      We confirmed that this novel combination therapy can effectively improve the survival and proliferation of NK cells\n                      <jats:italic>in vivo<\/jats:italic>\n                      , offering a safer and more effective way to enhance their therapeutic effects\n                      <jats:italic>in vivo<\/jats:italic>\n                      . This approach provides a solution to the challenges of the cumbersome\n                      <jats:italic>in vitro<\/jats:italic>\n                      gene modification of PBMC-derived NK cells and their insufficient therapeutic\n                      <jats:italic>in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1875554","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:42:52Z","timestamp":1788417772000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["PBMC-derive eNK cells was armed and promoted CAR-like response against tumors through armed with 16Fc21, a novel bispecific fusion protein for NK cells"],"prefix":"10.3389","volume":"17","author":[{"given":"Yangyang","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Advanced Technology, University of Science and 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