Antigen-Clustered Nanovaccine Achieves Long-Term Tumor Remission by Promoting B/CD 4 T Cell Crosstalk.
In: ACS nano, Jg. 18 (2024-04-02), Heft 13, S. 9584-9604
academicJournal
Zugriff:
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.
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Antigen-Clustered Nanovaccine Achieves Long-Term Tumor Remission by Promoting B/CD 4 T Cell Crosstalk.
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Autor/in / Beteiligte Person: | Li, C ; Clauson, R ; Bugada, LF ; Ke, F ; He, B ; Yu, Z ; Chen, H ; Jacobovitz, B ; Hu, H ; Chuikov, P ; Hill, BD ; Rizvi, SM ; Song, Y ; Sun, K ; Axenov, P ; Huynh, D ; Wang, X ; Garmire, L ; Lei, YL ; Grigorova, I ; Wen, F ; Cascalho, M ; Gao, W ; Sun, D |
Zeitschrift: | ACS nano, Jg. 18 (2024-04-02), Heft 13, S. 9584-9604 |
Veröffentlichung: | Washington D.C. : American Chemical Society, 2024 |
Medientyp: | academicJournal |
ISSN: | 1936-086X (electronic) |
DOI: | 10.1021/acsnano.3c13038 |
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