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SFV 基 RNA 复制子癌症疫苗治疗 HPV 诱导性癌症的首例人体临床 I 期试验。

First-in-Human Phase I Clinical Trial of an SFV-Based RNA Replicon Cancer Vaccine against HPV-Induced Cancers.

机构信息

Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

出版信息

Mol Ther. 2021 Feb 3;29(2):611-625. doi: 10.1016/j.ymthe.2020.11.002. Epub 2020 Nov 5.

DOI:10.1016/j.ymthe.2020.11.002
PMID:33160073
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7854293/
Abstract

A first-in-human phase I trial of Vvax001, an alphavirus-based therapeutic cancer vaccine against human papillomavirus (HPV)-induced cancers was performed assessing immunological activity, safety, and tolerability. Vvax001 consists of replication-incompetent Semliki Forest virus replicon particles encoding HPV16-derived antigens E6 and E7. Twelve participants with a history of cervical intraepithelial neoplasia were included. Four cohorts of three participants were treated per dose level, ranging from 5 × 10 to 2.5 × 10 infectious particles per immunization. The participants received three immunizations with a 3-week interval. For immune monitoring, blood was drawn before immunization and 1 week after the second and third immunization. Immunization with Vvax001 was safe and well tolerated, with only mild injection site reactions, and resulted in both CD4 and CD8 T cell responses against E6 and E7 antigens. Even the lowest dose of 5 × 10 infectious particles elicited E6/E7-specific interferon (IFN)-γ responses in all three participants in this cohort. Overall, immunization resulted in positive vaccine-induced immune responses in 12 of 12 participants in one or more assays performed. In conclusion, Vvax001 was safe and induced immune responses in all participants. These data strongly support further clinical evaluation of Vvax001 as a therapeutic vaccine in patients with HPV-related malignancies.

摘要

Vvax001 是一种基于甲病毒的治疗性癌症疫苗，用于对抗人乳头瘤病毒（HPV）引起的癌症。这是首次进行人体 I 期临床试验，旨在评估其免疫活性、安全性和耐受性。Vvax001 由复制缺陷型 Semliki Forest 病毒复制子颗粒组成，编码 HPV16 衍生的抗原 E6 和 E7。该研究纳入了 12 名有宫颈上皮内瘤变病史的参与者。每个剂量组有 3 名参与者，共分为 4 个队列，免疫接种剂量分别为 5×10 至 2.5×10 个感染性颗粒。参与者每 3 周接受一次免疫接种，共 3 次。为了进行免疫监测，在免疫接种前和第二次及第三次免疫接种后 1 周采集血液样本。Vvax001 免疫接种安全且耐受性良好，仅出现轻微的注射部位反应，可诱导针对 E6 和 E7 抗原的 CD4 和 CD8 T 细胞反应。即使在最低剂量 5×10 个感染性颗粒组，该队列的所有 3 名参与者均产生了针对 E6/E7 的干扰素（IFN）-γ 反应。总体而言，12 名参与者中有 12 名在一项或多项检测中产生了阳性的疫苗诱导免疫反应。总之，Vvax001 安全且可诱导所有参与者产生免疫反应。这些数据强烈支持进一步在 HPV 相关恶性肿瘤患者中评估 Vvax001 作为治疗性疫苗的临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41d/7854293/44edceb86a35/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41d/7854293/5f7f31088dd4/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41d/7854293/6a3a94d16708/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41d/7854293/d6f2c6a2ddb5/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41d/7854293/63fa65dc266e/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41d/7854293/2aa08180c2c6/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41d/7854293/44edceb86a35/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41d/7854293/5f7f31088dd4/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41d/7854293/6a3a94d16708/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41d/7854293/d6f2c6a2ddb5/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41d/7854293/63fa65dc266e/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41d/7854293/2aa08180c2c6/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d41d/7854293/44edceb86a35/gr5.jpg

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