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晚期结肠癌对肽疫苗治疗的显著临床反应:一例病例报告

Significant clinical response of advanced colon cancer to peptide vaccine therapy: a case report.

作者信息

Yasuda Seiei, Tsuchiya Izumi, Okada Kazutake, Tanaka Akira, Suzuki Toshiyuki, Sadahiro Sotaro, Takeda Kazuyoshi, Yamamoto Soichiro, Nakui Minoru

机构信息

Department of Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.

出版信息

Tokai J Exp Clin Med. 2012 Jul 20;37(2):57-61.

Abstract

Partial response (PR) was obtained in a patient with advanced colon cancer following peptide vaccine therapy. A 61-year-old woman was referred to our hospital for peptide vaccine therapy. She had undergone sigmoidectomy at a nearby hospital and eventually developed multiple metastases to the lung and pelvic lymph nodes with left hydronephrosis. A ureteral stenting catheter had been inserted for left hydronephrosis, and oral opioids had been administered for relief of pain in the left pelvic region. Three tumor-antigen-derived peptides (RNF43, TOMM34, and KOC1) and two human VEGFR-derived peptides (VEGFR1 and VEGFR2) were used as a cocktail. The peptide cocktail was subcutaneously inoculated on days 1, 8, 15, and 22 and repeated at 14-day intervals. The patient's serum level of carcinoembryonic antigen was 28.9 ng/mL (N<5 ng/mL) before treatment, and it decreased promptly after the initiation of therapy to within a normal range. Evaluation of computed tomography images at week 5 revealed PR as determined by the Response Evaluation Criteria in Solid Tumor criteria. After month 3, the oral opioid was discontinued. The PR lasted for 4 months and was followed by stable disease for another 4 months. No particular adverse effects were observed. A cytotoxic T lymphocyte (CTL) response was evaluated by immunosorbent spot assay, and a positive CTL response was recognized against at least one of five peptides at each end of the six courses. Immunotherapy has been proven to slow tumor growth by inducing an active antitumor immune response; and therefore, significant tumor shrinkage is rarely observed. To our knowledge, this is the first case report of PR presented in a patient with advanced colon cancer.

摘要

一名晚期结肠癌患者在接受肽疫苗治疗后获得了部分缓解(PR)。一名61岁女性因肽疫苗治疗转诊至我院。她在附近医院接受了乙状结肠切除术,最终出现肺和盆腔淋巴结多发转移,并伴有左肾积水。已插入输尿管支架导管治疗左肾积水,并给予口服阿片类药物缓解左盆腔疼痛。三种肿瘤抗原衍生肽(RNF43、TOMM34和KOC1)和两种人血管内皮生长因子受体(VEGFR)衍生肽(VEGFR1和VEGFR2)混合使用。肽混合物分别在第1、8、15和22天皮下接种,并以14天为间隔重复接种。治疗前患者癌胚抗原血清水平为28.9 ng/mL(正常范围<5 ng/mL),治疗开始后迅速降至正常范围内。第5周计算机断层扫描图像评估显示,根据实体瘤疗效评价标准确定为部分缓解。3个月后,停用口服阿片类药物。部分缓解持续了4个月,随后疾病稳定又持续了4个月。未观察到特殊不良反应。通过免疫吸附斑点试验评估细胞毒性T淋巴细胞(CTL)反应,在六个疗程的每个疗程结束时,均识别出针对五种肽中至少一种的阳性CTL反应。免疫疗法已被证明可通过诱导积极的抗肿瘤免疫反应来减缓肿瘤生长;因此,很少观察到明显的肿瘤缩小。据我们所知,这是首例晚期结肠癌患者出现部分缓解的病例报告。

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