TY - JOUR
T1 - First-in-Human Phase I Clinical Trial of an SFV-Based RNA Replicon Cancer Vaccine against HPV-Induced Cancers
AU - Komdeur, Fenne L.
AU - Singh, Amrita
AU - van de Wall, Stephanie
AU - Meulenberg, Janneke J.M.
AU - Boerma, Annemarie
AU - Hoogeboom, Baukje Nynke
AU - Paijens, Sterre T.
AU - Oyarce, Cesar
AU - de Bruyn, Marco
AU - Schuuring, Ed
AU - Regts, Joke
AU - Marra, Ruben
AU - Werner, Naomi
AU - Sluis, Jessica
AU - van der Zee, Ate G.J.
AU - Wilschut, Jan C.
AU - Allersma, Derk P.
AU - van Zanten, Coba J.
AU - Kosterink, Jos G.W.
AU - Jorritsma-Smit, Annelies
AU - Yigit, Refika
AU - Nijman, Hans W.
AU - Daemen, Toos
PY - 2021/2/3
Y1 - 2021/2/3
N2 - 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 × 105 to 2.5 × 108 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 × 105 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. Komdeur, Singh, et al. report on a first-in-human phase I clinical trial of a Semliki Forest virus-based cancer vaccine. The trial shows that the vaccine is safe and well tolerated, inducing strong HPV16 E6- and E7-specific CD8 and CD4 T cell responses.
AB - 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 × 105 to 2.5 × 108 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 × 105 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. Komdeur, Singh, et al. report on a first-in-human phase I clinical trial of a Semliki Forest virus-based cancer vaccine. The trial shows that the vaccine is safe and well tolerated, inducing strong HPV16 E6- and E7-specific CD8 and CD4 T cell responses.
KW - alphavirus replicon vaccine
KW - cervical intraepithelial neoplasia
KW - human papillomavirus
KW - immunotherapy
KW - recombinant Semliki Forest virus vector
KW - therapeutic vaccine
KW - Vvax001
U2 - 10.1016/j.ymthe.2020.11.002
DO - 10.1016/j.ymthe.2020.11.002
M3 - Article
C2 - 33160073
AN - SCOPUS:85096393897
SN - 1525-0016
VL - 29
SP - 611
EP - 625
JO - Molecular Therapy
JF - Molecular Therapy
IS - 2
ER -