Affiliation:
1. State Key Laboratory of Physical Chemistry of Solid Surfaces Key Laboratory for Chemical Biology of Fujian Province The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation Department of Chemical Biology College of Chemistry and Chemical Engineering Xiamen University 361005 Xiamen Fujian China
2. Institute of Molecular Medicine Renji Hospital School of Medicine Shanghai Jiao Tong University 200127 Shanghai China
Abstract
AbstractThe percentage of low response and adaptive resistance to current antibody‐based immune checkpoint blockade (ICB) therapy requires the development of novel immunotherapy strategies. Here, we developed an aptamer‐assisted immune checkpoint blockade (Ap‐ICB) against sialic acid‐binding immunoglobulin‐like lectin‐15 (Siglec‐15), a novel immune suppressor broadly upregulated on cancer cells and tumor infiltrating myeloid cells, which is mutually exclusive of programmed cell death ligand 1 (PD‐L1). Using protein aptamer selection, we identified WXY3 aptamer with high affinity against Siglec‐15 protein/Siglec‐15 positive cells. We demonstrated that WXY3 aptamer rescued antigen‐specific T cell responses in vitro and in vivo. Importantly, the WXY3 Ap‐ICB against Siglec‐15 amplified anti‐tumor immunity in the tumor microenvironment and inhibited tumor growth/metastasis in syngeneic mouse model, which may result from enhanced macrophage and T cell functionality. In addition, by using aptamer‐based spherical nucleic acids, we developed a synergetic ICB strategy of multivalent binding and steric hindrance, which further improves the in vivo anti‐tumor effect. Taken together, our results support Ap‐ICB targeted Siglec‐15 as a potential strategy for normalization cancer immunotherapy.
Subject
General Chemistry,Catalysis
Cited by
1 articles.
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