Affiliation:
1. Department of Rheumatology and Immunology The Third Affiliated Hospital Southern Medical University Guangzhou 510665 China
2. CAS Key Laboratory of Bio Medical Diagnostics Suzhou Institute of Biomedical Engineering and Technology Chinese Academy of Sciences Suzhou 215163 China
3. School of Medicine South China University of Technology Guangzhou Guangdong 510006 China
4. CAS Key Laboratory of Nano‐Bio Interface Suzhou Institute of Nano‐Tech and NanoBionics Chinese Academy of Sciences Suzhou 215123 China
Abstract
AbstractThe establishment of effective antitumor immune responses of vaccines is mainly limited by insufficient priming tumor infiltration of T cells and immunosuppressive tumor microenvironment (TME). Targeting β‐adrenergic receptor (β‐AR) signaling exerts promising benefits on reversing the suppressive effects directly on T cells, but it appears to have considerably limited antitumor performance when combined with vaccine‐based immunotherapies. Herein, a tumor membrane‐coated nanoplatform for codelivery of adjuvant CpG and propranolol (Pro), a β‐AR inhibitor is designed. The biomimetic nanovaccine displayed an improved accumulation in lymph nodes and sufficient drug release, thereby inducing dendritic cell maturation and antigen presentation. Meanwhile, the integration of vaccination and blockade of β‐AR signaling not only promoted the priming of the naive CD8+ T cells and effector T cell egress from lymph nodes, but also alleviated the immunosuppressive TME by decreasing the frequency of immunosuppressive cells and increasing the tumor infiltration of B cells and NK cells. Consequently, the biomimetic nanovaccines outperformed greater prophylactic and therapeutic efficacy than nanovaccines without Pro encapsulation in B16‐F10 melanoma mice. Taken together, the work explored a biomimetic nanovaccine for priming tumor infiltration of T cells and immunosuppressive TME regulation, offering tremendous potential for a combined β‐AR signaling‐targeting strategy in cancer immunotherapy.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Jiangsu Province
Pilot Projects and Preparatory Actions
Subject
Biomaterials,Biotechnology,General Materials Science,General Chemistry
Cited by
15 articles.
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