Cancer Immunol Immunother

Purpose Through genome-wide expression profile analysis, hypoxia-inducible protein 2 (HIG2) has previously been identified as an oncoprotein involved in development/progression of renal cell carcinoma (RCC). We subsequently identified a highly immunogenic HLA-A*0201/0206-restricted epitope peptide (HIG2-9-4) corresponding to a part of HIG2 and applied it as a therapeutic vaccine. We conducted a phase I clinical trial using the HIG2-9-4 peptide for patients with advanced RCC. Materials and Methods Nine patients having HLA-A*0201 or HLA-A*0206 with metastatic or unresectable RCC after failure of the cytokine and/or tyrosine kinase inhibitor therapies were enrolled in this study. The patients received subcutaneous administration of the peptide as an emulsion form with Montanide ISA-51 VG once a week in a dose-escalation manner (doses of 0.5, 1.0, or 3.0 mg/body, 3 patients for each dose). The primary endpoint was safety, and the secondary endpoints were immunological and clinical responses. Results Vaccinations with HIG2-9-4 peptide could be well tolerated without any serious systemic adverse events. Peptide-specific cytotoxic T lymphocyte (CTL) responses were detected in eight of the nine patients. Doses of 1.0 or 3.0 mg/body seemed to induce a CTL response better than did a dose of 0.5 mg/body, although the number of patients was too small to draw a firm conclusion. The disease control rate (stable disease for ≥4 months) was 77.8 %, and the median progression-free survival time was 10.3 months. Conclusions HIG2-9-4 peptide vaccine treatment was tolerable and effectively induced peptide-specific CTLs in RCC patients. This novel peptide vaccine therapy for RCC is promising

Milan Ultrasound Criteria predict relapse of ulcerative colitis in remission

Introduction Bowel ultrasound is a non-invasive alternative to endoscopy for assessing the disease activity of ulcerative colitis; however, it is unclear whether bowel ultrasound can predict subsequent relapse from remission. Materials and Methods A retrospective cohort study enrolled patients with ulcerative colitis who underwent bowel ultrasound between July 2018 and July 2021 during clinical remission (patient-reported outcome-2 ≤ 1 and no rectal bleeding) for at least 3 months and were followed up for 1 year. Ultrasonographic findings (bowel wall thickness, bowel wall flow, bowel wall stratification, and enlarged lymph nodes), Milan Ultrasound Criteria, Mayo endoscopic subscore, C-reactive protein, and fecal calprotectin levels and their association with subsequent clinical relapse were assessed. Relapse was defined as rectal bleeding score ≥ 1, stool frequency score ≥ 2, or treatment intensification for symptoms. Results 31% of the patients (18/58) relapsed within 1 year. No single ultrasonographic finding predicted relapse, whereas Milan Ultrasound Criteria > 6.2 (p = 0.019), Mayo endoscopic subscore ≥ 1 (p = 0.013), and fecal calprotectin ≥ 250 μg/g (p = 0.040) were associated with a shorter time to relapse in the log-rank test. Milan Ultrasound Criteria > 6.2 (hazard ratio 3.22; 95% confidence interval 1.14-9.08, p = 0.027) and Mayo endoscopic subscore ≥ 1 (hazard ratio 8.70; 95% confidence interval 1.11-68.1, p = 0.039) showed a higher risk of relapse according to a Cox proportional hazards model. Discussion/Conclusion Bowel ultrasound can predict subsequent clinical relapse from remission in patients with ulcerative colitis using the Milan Ultrasound Criteria