%0 Journal Article
%T Development of an mRNA-based therapeutic vaccine mHTV-03E2 for high-risk HPV-related malignancies.
%A Wang J
%A Wang Q
%A Ma L
%A Lv K
%A Han L
%A Chen Y
%A Zhou R
%A Zhou H
%A Chen H
%A Wang Y
%A Zhang T
%A Yi D
%A Liu Q
%A Zhang Y
%A Li X
%A Cheng T
%A Zhang J
%A Huang C
%A Dong Y
%A Zhang W
%A Cen S
%J Mol Ther
%V 32
%N 7
%D 2024 Jul 3
%M 38715363
%F 12.91
%R 10.1016/j.ymthe.2024.04.036
%X Human papillomavirus (HPV) 16 and 18 infections are related to many human cancers. Despite several preventive vaccines for high-risk (hr) HPVs, there is still an urgent need to develop therapeutic HPV vaccines for targeting pre-existing hrHPV infections and lesions. In this study, we developed a lipid nanoparticle (LNP)-formulated mRNA-based HPV therapeutic vaccine (mHTV)-03E2, simultaneously targeting the E2/E6/E7 of both HPV16 and HPV18. mHTV-03E2 dramatically induced antigen-specific cellular immune responses, leading to significant CD8+ T cell infiltration and cytotoxicity in TC-1 tumors derived from primary lung epithelial cells of C57BL/6 mice expressing HPV E6/E7 antigens, mediated significant tumor regression, and prolonged animal survival, in a dose-dependent manner. We further demonstrated significant T cell immunity against HPV16/18 E6/E7 antigens for up to 4 months post-vaccination in immunological and distant tumor rechallenging experiments, suggesting robust memory T cell immunity against relapse. Finally, mHTV-03E2 synergized with immune checkpoint blockade to inhibit tumor growth and extend animal survival, indicating the potential in combination therapy. We conclude that mHTV-03E2 is an excellent candidate therapeutic mRNA vaccine for treating malignancies caused by HPV16 or HPV18 infections.