TY - JOUR
T1 - Antigen-Clustered Nanovaccine Achieves Long-Term Tumor Remission by Promoting B/CD 4 T Cell Crosstalk
AU - Li, Chengyi
AU - Clauson, Ryan
AU - Bugada, Luke F.
AU - Ke, Fang
AU - He, Bing
AU - Yu, Zhixin
AU - Chen, Hongwei
AU - Jacobovitz, Binyamin
AU - Hu, Hongxiang
AU - Chuikov, Polina
AU - Hill, Brett Dallas
AU - Rizvi, Syed M.
AU - Song, Yudong
AU - Sun, Kai
AU - Axenov, Pasieka
AU - Huynh, Daniel
AU - Wang, Xinyi
AU - Garmire, Lana
AU - Lei, Yu Leo
AU - Grigorova, Irina
AU - Wen, Fei
AU - Cascalho, Marilia
AU - Gao, Wei
AU - Sun, Duxin
N1 - Publisher Copyright:
© 2024 American Chemical Society.
PY - 2024/4/2
Y1 - 2024/4/2
N2 - Current cancer vaccines using T cell epitopes activate antitumor T cell immunity through dendritic cell/macrophage-mediated antigen presentation, but they lack the ability to promote B/CD4 T cell crosstalk, limiting their anticancer efficacy. We developed antigen-clustered nanovaccine (ACNVax) to achieve long-term tumor remission by promoting B/CD4 T cell crosstalk. The topographic features of ACNVax were achieved using an iron nanoparticle core attached with an optimal number of gold nanoparticles, where the clusters of HER2 B/CD4 T cell epitopes were conjugated on the gold surface with an optimal intercluster distance of 5-10 nm. ACNVax effectively trafficked to lymph nodes and cross-linked with BCR, which are essential for stimulating B cell antigen presentation-mediated B/CD4 T cell crosstalk in vitro and in vivo. ACNVax, combined with anti-PD-1, achieved long-term tumor remission (>200 days) with 80% complete response in mice with HER2+ breast cancer. ACNVax not only remodeled the tumor immune microenvironment but also induced a long-term immune memory, as evidenced by complete rejection of tumor rechallenge and a high level of antigen-specific memory B, CD4, and CD8 cells in mice (>200 days). This study provides a cancer vaccine design strategy, using B/CD4 T cell epitopes in an antigen clustered topography, to achieve long-term durable anticancer efficacy through promoting B/CD4 T cell crosstalk.
AB - Current cancer vaccines using T cell epitopes activate antitumor T cell immunity through dendritic cell/macrophage-mediated antigen presentation, but they lack the ability to promote B/CD4 T cell crosstalk, limiting their anticancer efficacy. We developed antigen-clustered nanovaccine (ACNVax) to achieve long-term tumor remission by promoting B/CD4 T cell crosstalk. The topographic features of ACNVax were achieved using an iron nanoparticle core attached with an optimal number of gold nanoparticles, where the clusters of HER2 B/CD4 T cell epitopes were conjugated on the gold surface with an optimal intercluster distance of 5-10 nm. ACNVax effectively trafficked to lymph nodes and cross-linked with BCR, which are essential for stimulating B cell antigen presentation-mediated B/CD4 T cell crosstalk in vitro and in vivo. ACNVax, combined with anti-PD-1, achieved long-term tumor remission (>200 days) with 80% complete response in mice with HER2+ breast cancer. ACNVax not only remodeled the tumor immune microenvironment but also induced a long-term immune memory, as evidenced by complete rejection of tumor rechallenge and a high level of antigen-specific memory B, CD4, and CD8 cells in mice (>200 days). This study provides a cancer vaccine design strategy, using B/CD4 T cell epitopes in an antigen clustered topography, to achieve long-term durable anticancer efficacy through promoting B/CD4 T cell crosstalk.
KW - B cell antigen presentation
KW - B/CD4 T cell crosstalk
KW - Cancer vaccine
KW - Tertiary lymphoid structures
KW - anti-PD-1/PD-L1 immunotherapy
KW - long-term antigen-specific memory B cells and T cells
KW - tumor immune microenvironment
UR - https://www.scopus.com/pages/publications/85188555434
U2 - 10.1021/acsnano.3c13038
DO - 10.1021/acsnano.3c13038
M3 - 文章
C2 - 38513119
AN - SCOPUS:85188555434
SN - 1936-0851
VL - 18
SP - 9584
EP - 9604
JO - ACS Nano
JF - ACS Nano
IS - 13
ER -
