{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kunika MD"],"funding":["National Institutes of Health National Cancer Institute","American Cancer Society","NCI NIH HHS","US Department of Veterans Affairs","CSRD VA"],"pagination":["112436"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12084002"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["28(5)"],"pubmed_abstract":["Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine carcinoma, and immune checkpoint inhibitors (ICIs) are the only approved therapy; nonetheless, resistance is notable and there is a critical need for novel effective therapies. Recently, CD276 was identified as a promising therapeutic target in human cancers. In preclinical studies, a modified CD276 antibody-drug conjugate (ADC) with pyrrolobenzodiazepine (m276-SL-PBD) elicited more potent anti-tumor effects than two CD276 ADCs currently in clinical trials. Here, we uncover notable CD276 expression in MCC patient tumors, and demonstrate m276-SL-PBD efficacy against MCC preclinical models. Complete eradication is observed in all xenografts bearing CD276 expression, with 82% achieving 180-day tumor-free survival after 4 or 5 weekly doses, and m276-SL-PBD remained efficacious against relapsed tumors. Of clinical relevance, m276-SL-PBD retains its potency in MCC-bearing humanized mice. Importantly, no detectable adverse effects were observed. Thus, m276-SL-PBD is a promising therapy for patients unsuitable or resistant to ICIs."],"journal":["iScience"],"pubmed_title":["m276-SL-PBD eradicates tumors and instigates long-lasting tumor-free survival in Merkel cell carcinoma preclinical models."],"pmcid":["PMC12084002"],"funding_grant_id":["I01 CX002497","R01 CA266514"],"pubmed_authors":["Kannan A","Velasco GJ","Pham D","Lambrecht N","Seaman S","Das BK","Feng Y","Gao L","Kunika MD","St Croix B","Zhao H"],"additional_accession":[]},"is_claimable":false,"name":"m276-SL-PBD eradicates tumors and instigates long-lasting tumor-free survival in Merkel cell carcinoma preclinical models.","description":"Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine carcinoma, and immune checkpoint inhibitors (ICIs) are the only approved therapy; nonetheless, resistance is notable and there is a critical need for novel effective therapies. Recently, CD276 was identified as a promising therapeutic target in human cancers. In preclinical studies, a modified CD276 antibody-drug conjugate (ADC) with pyrrolobenzodiazepine (m276-SL-PBD) elicited more potent anti-tumor effects than two CD276 ADCs currently in clinical trials. Here, we uncover notable CD276 expression in MCC patient tumors, and demonstrate m276-SL-PBD efficacy against MCC preclinical models. Complete eradication is observed in all xenografts bearing CD276 expression, with 82% achieving 180-day tumor-free survival after 4 or 5 weekly doses, and m276-SL-PBD remained efficacious against relapsed tumors. Of clinical relevance, m276-SL-PBD retains its potency in MCC-bearing humanized mice. Importantly, no detectable adverse effects were observed. Thus, m276-SL-PBD is a promising therapy for patients unsuitable or resistant to ICIs.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 May","modification":"2026-04-08T19:46:39.693Z","creation":"2026-04-08T14:28:38.636Z"},"accession":"S-EPMC12084002","cross_references":{"pubmed":["40384933"],"doi":["10.1016/j.isci.2025.112436"]}}