{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:12:55Z","timestamp":1786122775263,"version":"build-2736575974"},"reference-count":10,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"unspecified","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,7,27]]},"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:p>Natural killer (NK) cell-based immunotherapy is an increasingly important cancer treatment strategy because of its innate cytotoxicity, allogeneic potential, and compatibility with off-the-shelf manufacturing. We analyzed 287 clinical trials identified in the INFORMA database to characterize the global development of NK-cell therapies across phases, regions, indications, combinations, cell sources, product origins, and engineering platforms. Most trials were planned or early-phase, and combination regimens were more frequent than monotherapy. The USA, China, and South Korea led clinical activity. Hematologic malignancies remained the principal testing ground, while lung, colorectal, and other solid tumors reflected broader expansion. Platform-level analysis showed a predominance of allogeneic products and rapid growth of CAR-engineered NK-cell trials after 2020. These findings indicate a transition from proof-of-concept adoptive transfer toward standardized, genetically programmable, off-the-shelf platforms. The principal challenge is shifting from manufacturing feasibility alone to durable biological activity. Future development should align cell engineering, combination partners, translational endpoints, and biomarker-guided patient selection with specific barriers involving persistence, tumor delivery, microenvironmental fitness, and immune escape.<\/jats:p>","DOI":"10.1136\/jitc-2026-016348","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T11:55:16Z","timestamp":1786103716000},"page":"e016348","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical trial landscape and translational prospects of natural killer cell-based immunotherapy: an analysis based on the INFORMA database"],"prefix":"10.1136","volume":"14","author":[{"given":"Han","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Radiotherapy, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanni","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Machinery, General Hospital of Shenyang Coal Industry Group of Liaoning Health Industry Group, Shenyang, Liaoning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dehua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Interventional Therapy, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9829-4769","authenticated-orcid":false,"given":"Jinhan","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Interventional Therapy, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"2026080704550863000_14.8.e016348.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-020-0426-7"},{"key":"2026080704550863000_14.8.e016348.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-022-00491-0"},{"key":"2026080704550863000_14.8.e016348.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1910607"},{"key":"2026080704550863000_14.8.e016348.4","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S0140-6736(24)02462-0","article-title":"Induced pluripotent stem-cell-derived CD19-directed chimeric antigen receptor natural killer cells in B-cell lymphoma: a phase 1, first-in-human trial","volume":"405","author":"Ghobadi","year":"2025","journal-title":"Lancet"},{"key":"2026080704550863000_14.8.e016348.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02785-8"},{"key":"2026080704550863000_14.8.e016348.6","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1182\/blood.2021011532","article-title":"Systemic IL-15 promotes allogeneic cell rejection in patients treated with natural killer cell adoptive therapy","volume":"139","author":"Berrien-Elliott","year":"2022","journal-title":"Blood"},{"key":"2026080704550863000_14.8.e016348.7","doi-asserted-by":"crossref","DOI":"10.1186\/s40425-017-0275-9","article-title":"Genetic engineering of human NK cells to express CXCR2 improves migration to renal cell carcinoma","volume":"5","author":"Kremer","year":"2017","journal-title":"J Immunother Cancer"},{"key":"2026080704550863000_14.8.e016348.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.08.011"},{"key":"2026080704550863000_14.8.e016348.9","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao0505"},{"key":"2026080704550863000_14.8.e016348.10","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-2365"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2026-016348","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T11:55:17Z","timestamp":1786103717000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2026-016348"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":10,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8,7]]},"published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1136\/jitc-2026-016348"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2026-016348","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]}}}