{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T14:03:59Z","timestamp":1780581839518,"version":"3.54.1"},"reference-count":24,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"unspecified","delay-in-days":3,"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":[[2026,4,18]]},"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:p>Approximately one-third of patients with metastatic triple-negative breast cancer (TNBC) develop brain metastases during their lifetime. Notably, up to 90% of TNBC brain metastases express B7-H3, a molecule that contributes to an immunosuppressive microenvironment\u2014positively correlating with regulatory T cells and negatively with CD8+T cells. We propose that B7-H3-targeted antibody-drug conjugates (ADCs) may help convert these immunologically \u201ccold\u201d tumors into \u201chot\u201d ones, thereby enhancing the responsiveness of patients with metastatic TNBC and brain metastases to immunotherapy. The ability of ADCs to penetrate a blood-brain barrier that is disrupted by brain metastases and\/or associated local therapies generates considerable excitement for this potential approach.<\/jats:p>\n                  <jats:p>\n                    We further describe a search of the\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/clinicaltrials.gov\">clinicaltrials.gov<\/jats:ext-link>\n                    website, which yielded eight phase I\/II trials examining the efficacy of B7-H3 ADCs, 12.5% (n=1\/8) of which exclude patients with brain metastases and 62.5% (n=5\/8) of which include patients with asymptomatic brain metastases. Given the natural progression of metastatic TNBC and the high incidence of brain metastases, future studies of B7-H3-targeted therapies should consider the broad inclusion of patients with brain metastases. Additionally, the potential of B7-H3-targeted ADCs to prevent brain metastases warrants investigation in both preclinical models and clinical trials.\n                  <\/jats:p>","DOI":"10.1136\/jitc-2025-013907","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T13:20:17Z","timestamp":1780579217000},"page":"e013907","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting B7-H3 in patients with metastatic triple-negative breast cancer and brain metastases: an opportunity to \u201crevive\u201d immunotherapy as a treatment strategy?"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct03417544","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03449238","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03807765","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03807765","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Isabella","family":"Kojundzic","sequence":"first","affiliation":[{"name":"Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada"},{"name":"Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cody","family":"Zatzman","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada"},{"name":"Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Belone Lopes","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada"},{"name":"Department of Medicine, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohma","family":"Ramay","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Bayani","sequence":"additional","affiliation":[{"name":"Diagnostic Development, Ontario Institute for Cancer Research, Toronto, Ontario, Canada"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Spears","sequence":"additional","affiliation":[{"name":"Diagnostic Development, Ontario Institute for Cancer Research, Toronto, Ontario, Canada"},{"name":"Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna J","family":"Jerzak","sequence":"additional","affiliation":[{"name":"Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada"},{"name":"Department of Medicine, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"2026060406201356000_14.6.e013907.1","doi-asserted-by":"crossref","unstructured":"Chehade R , Qazi MA , Ennis M , et al . 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