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Inoculation with tumor cell membrane\u2010derived vaccines is a promising strategy to activate B cells, yet their efficiency is limited due to lack of costimulatory molecules. To amplify B cell responses against tumor, herein, a spatiotemporally\u2010synchronized antigen\u2010adjuvant integrated nanovaccine, termed as CM\u2010CpG\u2010aCD40, is constructed by conjugating the immune stimulative CpG oligonucleotide and the anti\u2010CD40 antibody (aCD40) onto the membrane vesicles derived from triple negative breast cancer cells. CM\u2010CpG\u2010aCD40 actively accumulates in lymph nodes and is effectively captured by antigen\u2010presenting cells via the recognition of CD40 by aCD40. Tumor antigens on CM\u2010CpG\u2010aCD40 bind to B cell receptors, providing the first stimulation signal for B cells. Meanwhile, the interaction between CpG\/Toll like receptor and aCD40\/CD40 provides superposed co\u2010stimulation signals, improving the antibody\u2010secreting and antigen\u2010presenting abilities of B cells. The nanovaccine also stimulates dendritic cells to activate CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, and reprograms tumor associated macrophages. CM\u2010CpG\u2010aCD40 activating humoral, cellular, and innate antitumor immunity achieves a tumor inhibition rate of 89.3%, which is further improved to 95.4% when combined with the anti\u2010programmed death ligand 1 (PD\u2010L1) antibody. CM\u2010CpG\u2010aCD40, as a personalized multi\u2010epitope nanovaccine, paves the way for ushering the era of B cell\u2010based immunotherapy.\n                  <\/jats:p>","DOI":"10.1002\/adma.202411361","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T04:06:25Z","timestamp":1734926785000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Personalized Multi\u2010Epitope Nanovaccine Unlocks B Cell\u2010Mediated Multiple Pathways of Antitumor Immunity"],"prefix":"10.1002","volume":"37","author":[{"given":"Wenlu","family":"Yan","sequence":"first","affiliation":[{"name":"State Key Laboratory of Drug Research &amp; Center of Pharmaceutics, Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai 201203 China"},{"name":"School of Pharmacy University of Chinese Academy of Sciences  Beijing 100049 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