Individualized neoantigen peptide immunization of a metastatic pancreatic cancer patient: a case report of combined tumor and liquid biopsy

Tim Roehnisch, Mari Carmen Martos-Contreras, Mehdi Manoochehri, Mauro Nogueira, Franziska Bremm, Jan Dörrie, Jan Christoph, Meik Kunz, W. Schönharting
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Abstract

This report details a case of pancreatic cancer with liver metastasis that exhibited a positive immune response to personalized immunization therapy. Our study involved the identification of neoantigens and their corresponding immunogenic peptides using an in-house bioinformatic pipeline. This process included the identification of somatic mutations through DNA/RNA sequencing of solid tumor tissue and blood liquid biopsy. Computational prediction techniques were then employed to identify novel epitopes, followed by the design and manufacture of patient-specific immunization peptides. In combination with standard-of-care chemotherapy, the patient received a sequence of 5 biweekly prime injections followed by 2 boost injections 2 and 5 months later. The peptides were emulsified in Montanide and the injection-site was conditioned with nivolumab and imiquimod. The combined regimen of peptide immunization and chemotherapy resulted in a notable decline in CA19-9 tumor marker levels following both prime and boost applications. Subsequent MRI assessments revealed a reduction in the size of liver metastases several months post-immunization initiation. Importantly, the patient showed and improved overall survival and reported an improved quality of life without experiencing significant treatment-related adverse effects. This case underscores the potential benefits of personalized peptide-based immunization as an adjunctive therapy in the treatment of advanced pancreatic cancer, showcasing promising outcomes in tumor marker reduction, tumor shrinkage, and enhanced patient well-being.
一名转移性胰腺癌患者的个体化新抗原肽免疫:肿瘤和液体活检联合病例报告
本报告详细介绍了一例胰腺癌肝转移病例,该病例对个性化免疫疗法产生了积极的免疫反应。我们的研究包括利用内部生物信息学管道鉴定新抗原及其相应的免疫原肽。这一过程包括通过对实体瘤组织和血液液体活检的DNA/RNA测序鉴定体细胞突变。然后采用计算预测技术识别新的表位,接着设计和制造患者特异性免疫肽。患者在接受标准化疗的同时,每两周进行5次基础注射,然后在2个月和5个月后进行2次加强注射。肽在蒙脱石散中乳化,注射部位用尼伐单抗和咪喹莫特调节。多肽免疫和化疗联合疗法使CA19-9肿瘤标志物水平在初次注射和加强注射后均显著下降。随后的核磁共振成像评估显示,免疫开始后数月,肝转移灶的大小有所缩小。重要的是,患者的总生存期得到了改善,生活质量也得到了提高,而且没有出现明显的治疗相关不良反应。该病例强调了基于多肽的个性化免疫作为晚期胰腺癌辅助疗法的潜在益处,展示了在肿瘤标志物减少、肿瘤缩小和提高患者生活质量方面的良好效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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