Preclinical Evaluation of a Replication-Deficient Recombinant Adenovirus Serotype 5 Vaccine Expressing Guanylate Cyclase C and the PADRE T-helper Epitope.

Q1 Immunology and Microbiology

Human Gene Therapy Methods Pub Date : 2016-12-01 DOI:10.1089/HGTB.2016.114

E. SnookAdam, R. BaybuttTrevor, HyslopTerry, A. WaldmanScott

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引用次数: 17

Abstract

There is an unmet need for improved therapeutics for colorectal cancer, the second leading cause of cancer mortality worldwide. Adjuvant chemotherapy only marginally improves survival in some patients and has no benefit in others, underscoring the clinical opportunity for novel immunotherapeutic approaches to improve survival in colorectal cancer. In that context, guanylate cyclase C (GUCY2C) is an established biomarker and therapeutic target for metastatic colorectal cancer with immunological characteristics that promote durable antitumor efficacy without autoimmunity. Preliminary studies established non-replicating human type 5 adenovirus (Ad5) expressing GUCY2C as safe and effective to induce GUCY2C-specific immune responses and antitumor immunity in mice. This study characterized the biodistribution, immunogenicity, and safety of a vector expressing GUCY2C fused with the human CD4+ T helper cell epitope PADRE (Ad5-GUCY2C-PADRE) to advance this vaccine into clinical trials in colorectal cancer patients...

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表达鸟苷酸环化酶C和PADRE t辅助表位的复制缺陷重组腺病毒血清5型疫苗的临床前评价

结直肠癌是全球癌症死亡的第二大原因，对改进治疗方法的需求尚未得到满足。辅助化疗只能略微提高一些患者的生存率，而对其他患者没有益处，这强调了新型免疫治疗方法提高结直肠癌患者生存率的临床机会。在这种背景下，鸟苷酸环化酶C (GUCY2C)是一种已建立的生物标志物和转移性结直肠癌的治疗靶点，具有促进无自身免疫的持久抗肿瘤疗效的免疫学特性。初步研究证实，表达GUCY2C的非复制型人5型腺病毒(Ad5)在诱导小鼠GUCY2C特异性免疫反应和抗肿瘤免疫方面是安全有效的。本研究鉴定了表达GUCY2C与人CD4+ T辅助细胞表位PADRE (Ad5-GUCY2C-PADRE)融合的载体的生物分布、免疫原性和安全性，以推进该疫苗在结直肠癌患者中的临床试验。

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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来源期刊

Human Gene Therapy Methods BIOTECHNOLOGY & APPLIED MICROBIOLOGY-GENETICS & HEREDITY

CiteScore

5.80

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Human Gene Therapy is the premier, multidisciplinary journal covering all aspects of gene therapy. The Journal publishes in-depth coverage of DNA, RNA, and cell therapies by delivering the latest breakthroughs in research and technologies. Human Gene Therapy provides a central forum for scientific and clinical information, including ethical, legal, regulatory, social, and commercial issues, which enables the advancement and progress of therapeutic procedures leading to improved patient outcomes, and ultimately, to curing diseases. The Journal is divided into three parts. Human Gene Therapy, the flagship, is published 12 times per year. HGT Methods, a bimonthly journal, focuses on the applications of gene therapy to product testing and development. HGT Clinical Development, a quarterly journal, serves as a venue for publishing data relevant to the regulatory review and commercial development of cell and gene therapy products.