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

被引：57

作者：

Komdeur, Fenne L. ^{[1
]}

Singh, Amrita ^{[2
]}

van de Wall, Stephanie ^{[2
]}

Meulenberg, Janneke J. M. ^{[3
]}

Boerma, Annemarie ^{[2
]}

Hoogeboom, Baukje Nynke ^{[2
]}

Paijens, Sterre T. ^{[1
]}

Oyarce, Cesar ^{[2
]}

de Bruyn, Marco ^{[1
]}

Schuuring, Ed ^{[4
]}

Regts, Joke ^{[2
]}

Marra, Ruben ^{[2
]}

Werner, Naomi ^{[4
]}

Sluis, Jessica ^{[1
]}

van der Zee, Ate G. J. ^{[1
]}

Wilschut, Jan C. ^{[2
]}

Allersma, Derk P. ^{[5
]}

van Zanten, Coba J. ^{[5
]}

Kosterink, Jos G. W. ^{[5
]}

Jorritsma-Smit, Annelies ^{[4
]}

Yigit, Refika ^{[1
]}

Nijman, Hans W. ^{[1
]}

Daemen, Toos ^{[2
]}

机构：

[1] Univ Groningen, Univ Med Ctr Groningen, Dept Obstet & Gynecol, Groningen, Netherlands

[2] Univ Groningen, Univ Med Ctr Groningen, Dept Med Microbiol & Infect Prevent, POB 30-001,HPC EB88, NL-9700 RB Groningen, Netherlands

[3] ViciniVax BV, Meditech Ctr, Groningen, Netherlands

[4] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol, Groningen, Netherlands

[5] Univ Groningen, Univ Med Ctr Groningen, Dept Clin Pharm & Pharmacol, Groningen, Netherlands

来源：

MOLECULAR THERAPY | 2021年 / 29卷 / 02期

关键词：

SEMLIKI-FOREST-VIRUS; PAPILLOMAVIRUS TYPE-16 E6; CD4(+) T-CELLS; CERVICAL-CANCER; FUSION PROTEIN; IMMUNE-RESPONSES; DNA VACCINE; IMMUNIZATION; ALPHAVIRUS; INFECTION;

D O I：

10.1016/j.ymthe.2020.11.002

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

A first-in-human phase I trial of Vvax001, an alphavirusbased 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 x 10(5) to 2.5 x 10(8) 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 x 10(5) infectious particles elicited E6/E7-specific interferon (IFN)-gamma 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.

引用

页码：611 / 625

页数：15

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