mRNA vaccines in cancer clinical trials: HPV16 tumor-derived antigens (e6 and e7 oncoproteins) associated with head and neck squamous cell carcinoma (HNSCC), oropharyngeal and cervical cancers

SIMÕES, R.S.Q
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Abstract

Human papillomavirus (HPV) induces the most common sexually transmitted disease and has been classified in the Alphapapillomavirus genus, Papillomaviridae family. They are non‒enveloped viruses presenting a closed circular double‒stranded non‒segmented DNA genome of approximately 8 kb that infect the anogenital epithelium causing cervical cancer, anal and penis cancer. There are viral groups based on their oncogenic activity as high‒risk types, low‒risk types and types of undetermined‒risk. mRNA vaccines are being evaluated in people with HPV-related cancers. This study described how mRNA cancer vaccines work and their applications recruiting several strategies for HPV cancer immunotherapy. Several biopharmaceuticals are developing mRNA vaccines encoding neoepitopes that can induce immune responses against target tumors. One trial is testing a personalized mRNA vaccine in combination with an immune checkpoint inhibitor in patients with advanced head and neck cancer. The production of therapeutic mRNA proteins for development of vaccine cancer have been manufactured by upstream and downstream methods. Several stages are processed in bioreactors using input and output parameters to measure the quality control of purified substance. Thus, novel technologies using different mRNA delivery system can be able to be integrated in clinical trials of HPV16 tumor-derived antigens associated cervical intraepithelial lesions of different stages until head and neck squamous cell carcinoma, oropharyngeal and cervical cancers.
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癌症临床试验中的 mRNA 疫苗:与头颈部鳞状细胞癌 (HNSCC)、口咽癌和宫颈癌相关的 HPV16 肿瘤衍生抗原(e6 和 e7 肿瘤蛋白
人类乳头瘤病毒(HPV)是最常见的性传播疾病,被归类为乳头瘤病毒科 Alphapapillomavirus 属。它们是无包膜病毒,具有约 8 kb 的封闭环状双链非片段 DNA 基因组,可感染肛门上皮细胞,导致宫颈癌、肛门癌和阴茎癌。根据其致癌活性,病毒可分为高危型、低危型和风险未定型。这项研究描述了 mRNA 癌症疫苗的工作原理及其应用,并介绍了几种 HPV 癌症免疫疗法策略。几家生物制药公司正在开发编码新表位的 mRNA 疫苗,这些新表位可诱导针对目标肿瘤的免疫反应。一项试验正在晚期头颈癌患者中测试个性化 mRNA 疫苗与免疫检查点抑制剂的联合应用。用于开发癌症疫苗的治疗用 mRNA 蛋白的生产采用上游和下游方法。在生物反应器中使用输入和输出参数对多个阶段进行处理,以衡量纯化物质的质量控制。因此,使用不同 mRNA 运送系统的新技术可用于与不同阶段宫颈上皮内病变相关的 HPV16 肿瘤衍生抗原的临床试验,直至头颈部鳞状细胞癌、口咽癌和宫颈癌。
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