Antigen-Clustered Nanovaccine Achieves Long-Term Tumor Remission by Promoting B/CD 4 T Cell Crosstalk.

Autor:	Li C; Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States., Clauson R; Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States., Bugada LF; Department of Chemical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States., Ke F; Department of Microbiology and Immunology, Medical School, University of Michigan, Ann Arbor, Michigan 48109, United States., He B; Department of Computational Medicine & Bioinformatics, Medical School, University of Michigan, Ann Arbor, Michigan 48109, United States., Yu Z; Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States., Chen H; Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States., Jacobovitz B; Microscopy Core, Medical School, University of Michigan, Ann Arbor, Michigan 48109, United States., Hu H; Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States., Chuikov P; Department of Microbiology and Immunology, Medical School, University of Michigan, Ann Arbor, Michigan 48109, United States., Hill BD; Department of Chemical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States., Rizvi SM; Department of Chemical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States., Song Y; Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States., Sun K; Department of Materials Science and Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States., Axenov P; Department of Microbiology and Immunology, Medical School, University of Michigan, Ann Arbor, Michigan 48109, United States., Huynh D; Department of Microbiology and Immunology, Medical School, University of Michigan, Ann Arbor, Michigan 48109, United States., Wang X; Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States., Garmire L; Department of Computational Medicine & Bioinformatics, Medical School, University of Michigan, Ann Arbor, Michigan 48109, United States., Lei YL; Departments of Head and Neck Surgery, Cancer Biology, and Translational Molecular Pathology, the University of Texas M.D. Anderson Cancer Center, Houston, Texas 77054, United States., Grigorova I; Department of Microbiology and Immunology, Medical School, University of Michigan, Ann Arbor, Michigan 48109, United States., Wen F; Department of Chemical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States., Cascalho M; Department of Microbiology and Immunology, Medical School, University of Michigan, Ann Arbor, Michigan 48109, United States., Gao W; Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States., Sun D; Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States.
Jazyk:	angličtina
Zdroj:	ACS nano [ACS Nano] 2024 Apr 02; Vol. 18 (13), pp. 9584-9604. Date of Electronic Publication: 2024 Mar 21.
DOI:	10.1021/acsnano.3c13038
Abstrakt:	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.
Databáze:	MEDLINE
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