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

Authors

Chengyi Li
Ryan Clauson
Luke F Bugada
Fang Ke
Bing He
Zhixin Yu
Hongwei Chen
Binyamin Jacobovitz
Hongxiang Hu
Polina Chuikov
Brett Dallas Hill
Syed M Rizvi
Yudong Song
Kai Sun
Pasieka Axenov
Daniel Huynh
Xinyi Wang
Lana Garmire
Yu Leo Lei
Irina Grigorova
Fei Wen
Marilia Cascalho
Wei Gao
Duxin Sun

Publication Date

4-2-2024

Journal

ACS Nano

Abstract

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.

Keywords

Cancer vaccine, B cell antigen presentation, B/CD4 T cell crosstalk, tumor immune microenvironment, anti-PD-1/PD-L1 immunotherapy, long-term antigen-specific memory B cells and T cells, Tertiary lymphoid structures

Comments

Supplementary Material

Data Availability Statement

PMID: 38513119

DOI

10.1021/acsnano.3c13038

PMID

38513119

PMCID

PMC11130742

PubMedCentral® Posted Date

May 2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes