演題

Future biomarkers for immunotherapy:From the results of phase I and II study of five therapeutic peptides for advanced colorectal cancer

[演者] 硲 彰一:1
[著者] 井上 由佳:1, 兼清 信介:1, 新藤 芳太郎:1, 鈴木 伸明:1, 吉野 茂文:1, 中村 祐輔:2, 杉浦 史哲:3, 奥野 清隆:3, 藤田 知信:4, 田中 浩明:5, 田原 浩:6, 清水 良一:7, 衛藤 隆一:7, 小佐々 博明:7, 西村 拓:8, 坂田 晃一朗:8, 古谷 卓三:9, 河上 裕:4, 岡 正朗:10
1:山口大学消化器・腫瘍外科, 2:シカゴ大学内科・外科, 3:近畿大学外科, 4:慶應義塾大学先端医科学研究所細胞情報部門, 5:大阪市立大学腫瘍外科, 6:済生会呉病院外科, 7:小郡第一総合病院外科, 8:社会保険下関厚生病院消化器外科, 9:国立病院関門医療センター外科, 10:山口大学

Background: Biomarkers to predict the efficacy of immunotherapy have been awaited. A phase I/II study of five therapeutic epitope-peptides for advanced colorectal cancer (CRC) using five novel HLA-A*2402-binding peptides. We explored the predictive biomarker for the response to immunotherapy.Methods: Each of the five peptides (3 mg) was mixed with 1.5 ml of IFA and subcutaneously administered weekly for 12 weeks and after then biweekly. In the phase II study, chemotherapy was performed simultaneously as mFOLFOX6 (n=93) or XELOX (n=3) with bevacizumab (n=5). All enrolled pts had received the therapy without knowing HLA-A status double-blindly, and the HLA-A genotypes were key-opened at analysis point. Pretreatment serum IL-6 and CRP, lymphocyte%, neutrophil/lymphocyte (N/L) ratio and comprehensive expression profiles microRNA of the tumor were evaluated between HLA-A*2402 positive group and negative group. Results: IL-6 <1.0 (pg/ml) and Lymphocyte% >15% were the significant predictive markers (p=0.007, 0.034) for the long survival, which was observed only in HLA-A*2402 positive group. In the patients with IL-6 <1.0 or lymphocyte% >15, obvious trend to long survival in HLA-A*2402 positive group was observed. MiR-a and miR-b were selected for the predictive biomarkers. Patients with low miR-a or low miR-b were significantly survived longer than high miR groups which significances were observer only in HLA-A*2402 group. Conclusions: IL-6, Lymphocyte%, and miRs expression were the predictive biomarkers for the response to peptides vaccine and the selection of patients.
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