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To address this limitation, we conducted an investigator\u2010initiated, single\u2010center clinical trial (ChiCTR2300067818) evaluating the safety, feasibility, and preliminary efficacy of sequential personalized neoantigen vaccination following TACE plus TKI\/PD\u20101\u2010based therapy in patients with advanced HCC. Whole\u2010exome and transcriptome sequencing identified patient\u2010specific neoantigens, which were synthesized as long peptides and formulated with dual adjuvants for subcutaneous administration. Among 10 initially enrolled patients, 4 received personalized vaccination after comprehensive screening, with 2 patients (N03 and N04) completing the full 8\u2010injection vaccination regimen. Sequential neoantigen vaccination demonstrated excellent safety profiles, with only mild injection\u2010site reactions observed. Both patients achieved partial response following vaccination. Interferon\u2010gamma Enzyme\u2010Linked ImmunoSpot assays confirmed robust neoantigen\u2010specific responses against multiple peptide pools in both patients. Dynamic monitoring revealed that serum alpha\u2010fetoprotein and Des\u2010gamma\u2010carboxy prothrombin levels correlated with clinical responses, declining significantly during vaccination. These findings demonstrate that sequential personalized neoantigen vaccination following first\u2010line TACE\u2010based therapy is safe, feasible, and capable of inducing potent tumor\u2010specific immune responses, supporting further investigation in larger clinical trials.<\/jats:p>","DOI":"10.1002\/ijc.70445","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T03:31:47Z","timestamp":1773718307000},"page":"709-718","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sequential personalized neoantigen vaccination following first\u2010line treatments demonstrates safety and efficacy in advanced hepatocellular carcinoma"],"prefix":"10.1002","volume":"159","author":[{"given":"Zhixiong","family":"Cai","sequence":"first","affiliation":[{"name":"The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical 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