{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:31:35Z","timestamp":1790346695179,"version":"4.1.0"},"reference-count":42,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Department of Surgery Start-Up Grant City of Hope","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,3,7]]},"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Peritoneal metastasis (PM) from gastric cancer (GC) is associated with poor prognosis and limited treatment options. We investigated a novel peritoneal-targeted therapy using CF33-human sodium iodide symporter (hNIS), a chimeric orthopoxvirus, combined with anti-PD-L1 immune checkpoint blockade in an immunocompetent mouse model of GCPM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We evaluated replication and cytotoxicity of CF33-hNIS in human and murine GC cell lines. We assessed a syngeneic mouse model of PM using the transgenic mouse GC ACKPY3944 cells to test the efficacy of intraperitoneal (IP) CF33-hNIS alone and combined with intravenous or IP anti-PD-L1. Next, we performed flow cytometry and immunohistochemistry to analyze immune cell populations of CD3\n                      <jats:sup>+<\/jats:sup>\n                      T cell subsets in the peritoneal cavity and tumor microenvironment. Mice that showed complete tumor regression (CTR) were rechallenged with ACKPY3944 cells to assess memory T cell responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CF33-hNIS efficiently infected and killed GC cells. In vivo, IP CF33-hNIS alone significantly prolonged survival and increased infiltration of CD3\n                      <jats:sup>+<\/jats:sup>\n                      and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells within the peritoneal cavity and solid tumor. The most pronounced therapeutic effect was observed with a single high-dose of CF33-hNIS (10\n                      <jats:sup>8<\/jats:sup>\n                      plaque-forming units) combined with IP anti-PD-L1 (Combo 2) with 75% CTR. Notably, mice with CTR rejected tumor rechallenge, exhibiting significantly elevated effector and central memory T cell populations in the peritoneal cavity and spleen. IP CF33-hNIS demonstrates robust anti-tumor efficacy against GCPM, particularly when combined with IP anti-PD-L1 in the high-dose Combo 2 regimen.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings support a simplified, high-dose IP treatment strategy to overcome immune resistance in GCPM and provide a strong rationale for future clinical evaluation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-014530","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T15:40:42Z","timestamp":1775058042000},"page":"e014530","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Intraperitoneal CF33-hNIS combined with PD-L1 blockade eradicates gastric cancer peritoneal metastases and prevents recurrence via durable T cell 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