{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T02:50:46Z","timestamp":1780627846710,"version":"3.54.1"},"reference-count":27,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"unspecified","delay-in-days":19,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100025019","name":"Support for Pioneering Research Initiated by the Next Generation","doi-asserted-by":"publisher","award":["JPMJSP2136"],"award-info":[{"award-number":["JPMJSP2136"]}],"id":[{"id":"10.13039\/501100025019","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18H04060, 21H04832, 24H00643, 22H02923, 23K27460,"],"award-info":[{"award-number":["18H04060, 21H04832, 24H00643, 22H02923, 23K27460,"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["21453920, 24014825"],"award-info":[{"award-number":["21453920, 24014825"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,3,30]]},"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Natural killer (NK) cell-based immunotherapies remain largely ineffective against solid tumors and strategies that directly enhance NK cell cytotoxicity often fail to establish durable tumor control. To address this limitation, we developed GAIA-102, a novel NK-like phenotype with enhanced tumor-homing capacity, and its scalable derivative, expanded GAIA-102 (exp_GAIA). Here, we evaluated whether exp_GAIA can engage host immunity to drive durable response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A syngeneic lethal murine model of carcinomatous peritonitis was used to assess exp_GAIA. Following adoptive transfer of exp_GAIA with recombinant human interleukin-2 (rhIL-2), antitumor efficacy, survival and immune response were evaluated. Mechanistic studies quantified chemokine production and examined CCR5-dependent recruitment and expansion of endogenous NK cells, interferon-\u03b3 (IFN-\u03b3) secretion, and activation of tumor-specific CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells. Tumor immunogenic cell death (ICD) was assessed by calreticulin (CRT) surface translocation and analyzed for its association with endogenous NK expansion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Treatment with exp_GAIA plus rhIL-2 induced complete tumor regression and generated durable, tumor-specific adaptive immune response that required CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells. Mechanistically, exp_GAIA secreted CCR5-binding chemokines, particularly CCL3, thereby recruiting endogenous NK cells into tumor. Endogenous NK cells produced IFN-\u03b3, which activated tumor-specific CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells and established an innate-to-adaptive cytotoxicity axis. In parallel, exp_GAIA triggered tumor ICD characterized by CRT translocation, which further promoted in situ expansion of endogenous NK cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In combination with rhIL-2, exp_GAIA integrates endogenous NK activity with induction of long-lasting, CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell-dependent antitumor immunity via a CCR5-CCL3-NK-IFN-\u03b3-CD8 pathway, reinforced ICD with CRT exposure. These findings support exp_GAIA+rhIL-2 as a new NK-based strategy for durable control of solid tumors.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-014300","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T14:50:24Z","timestamp":1776696624000},"page":"e014300","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Novel NK cell-like phenotype expressing CCR5 and its ligands elicits tumor-specific acquired immunity to carcinomatous peritonitis via host NK-derived IFN-\u03b3"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct05608148","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05438459","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05207371","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05438459","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05922930","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05213195","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Situo","family":"Zheng","sequence":"first","affiliation":[{"name":"R&D Laboratory for Innovative Biotherapeutics, Graduate School of Pharmaceutical Sciences\uff0cKyushu University, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yui","family":"Harada","sequence":"additional","affiliation":[{"name":"R&D Laboratory for Innovative Biotherapeutics, Graduate School of Pharmaceutical Sciences\uff0cKyushu University, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Morodomi","sequence":"additional","affiliation":[{"name":"R&D Laboratory for Innovative Biotherapeutics, Graduate School of Pharmaceutical Sciences\uff0cKyushu University, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Yasuda","sequence":"additional","affiliation":[{"name":"R&D Laboratory for Innovative Biotherapeutics, Graduate School of Pharmaceutical Sciences\uff0cKyushu University, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenta","family":"Ishimoto","sequence":"additional","affiliation":[{"name":"R&D Laboratory for Innovative Biotherapeutics, Graduate School of Pharmaceutical Sciences\uff0cKyushu University, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1343-3927","authenticated-orcid":false,"given":"Yoshikazu","family":"Yonemitsu","sequence":"additional","affiliation":[{"name":"R&D Laboratory for Innovative Biotherapeutics, Graduate School of Pharmaceutical Sciences\uff0cKyushu University, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"2026042007501733000_14.4.e014300.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0052-1"},{"key":"2026042007501733000_14.4.e014300.2","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aaf2341","article-title":"Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia","volume":"8","author":"Romee","year":"2016","journal-title":"Sci Transl 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