Anti-TNFR2 enhanced the antitumor activity of a new HMGN1/3M-052 stimulated dendritic cell vaccine in a mouse model of colon cancer.

Lan Zhu, Xiangyan Zhang, Xin Chen, De Yang, Yujie Nie, Runsang Pan, Linzhao Li, Chenglv Wang, Huan Gui, Shuanghui Chen, Qianyu Jing, Mengjiao Wang, Yingjie Nie

Biochemical and biophysical research communications 2023 Apr 23

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Immunotherapy is the new approach for cancer treatment that can be achieved through several strategies, one of which is dendritic cells (DCs) vaccine therapy. However, traditional DC vaccination lacks accurate targeting, so DC vaccine preparation needs to be optimized. Immunosuppressive CD4+Foxp3+ regulatory T cells (Tregs) in the tumor microenvironment can promote tumor immune escape. Therefore, targeting Tregs has become a strategy for tumor immunotherapy. In this study, we found that HMGN1 (N1, a dendritic cell-activating TLR4 agonist) and 3M-052 (a newly synthesized TLR7/8 agonist) synergistically stimulate DCs maturation and increase the production of proinflammatory cytokines TNFα and IL-12. In a colon cancer mice model, vaccination with N1 and 3M-052 stimulated and tumor antigen-loaded DCs combined with anti-TNFR2 inhibited tumor growth in mice, and the antitumor effect was mainly achieved through stimulation of cytotoxic CD8 T cell activation and depletion of Tregs. Overall, the combinating of DC activation by N1 and 3M-052 with inhibition of Tregs by antagonizing TNFR2 as a therapeutic strategy may represent a more effective strategy for cancer treatment. Copyright © 2023 Elsevier Inc. All rights reserved.

Citation

Lan Zhu, Xiangyan Zhang, Xin Chen, De Yang, Yujie Nie, Runsang Pan, Linzhao Li, Chenglv Wang, Huan Gui, Shuanghui Chen, Qianyu Jing, Mengjiao Wang, Yingjie Nie. Anti-TNFR2 enhanced the antitumor activity of a new HMGN1/3M-052 stimulated dendritic cell vaccine in a mouse model of colon cancer. Biochemical and biophysical research communications. 2023 Apr 23;653:106-114