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

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

doi:10.1016/j.bbrc.2023.02.039

Cited by 6 publications

(3 citation statements)

References 38 publications

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“… 23 Our preliminary studies demonstrated that combining HMGN1 and 3M-052 with an anti-TNFR2-stimulated DC vaccine can effectively enhance the activation of CTLs by targeting Treg cells and immature DCs. 39 This dual-targeted immunosuppression approach results in homologous immune memory and effective antitumor effects. 39 As a result, we employed an immunotherapy combination along with a nanodelivery method, and the outcomes met our expectations.…”

Section: Discussionmentioning

confidence: 99%

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Regulating Tumor-Associated Macrophage Polarization by Cyclodextrin-Modified PLGA Nanoparticles Loaded with R848 for Treating Colon Cancer

Yuan,

Gui,

Chen

et al. 2024

IJN

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Purpose This study aimed to develop a novel and feasible modification strategy to improve the solubility and antitumor activity of resiquimod (R848) by utilizing the supramolecular effect of 2-hydroxypropyl-beta-cyclodextrin (2-HP-β-CD). Methods R848-loaded PLGA nanoparticles modified with 2-HP-β-CD (CD@R848@NPs) were synthesized using an enhanced emulsification solvent-evaporation technique. The nanoparticles were then characterized in vitro by several methods, such as scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, particle size analysis, and zeta potential analysis. Then, the nanoparticles were loaded with IR-780 dye and imaged using an in vivo imaging device to evaluate their biodistribution. Additionally, the antitumor efficacy and underlying mechanism of CD@R848@NPs in combination with an anti-TNFR2 antibody were investigated using an MC-38 colon adenocarcinoma model in vivo. Results The average size of the CD@R848@NPs was 376 ± 30 nm, and the surface charge was 21 ± 1 mV. Through this design, the targeting ability of 2-HP-β-CD can be leveraged and R848 is delivered to tumor-supporting M2-like macrophages in an efficient and specific manner. Moreover, we used an anti-TNFR2 antibody to reduce the proportion of Tregs. Compared with plain PLGA nanoparticles or R848, CD@R848@NPs increased penetration in tumor tissues, dramatically reprogrammed M1-like macrophages, removed tumors and prolonged patient survival. Conclusion The new nanocapsule system is a promising strategy for targeting tumor, reprogramming tumor -associated macrophages, and enhancement immunotherapy.

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Section: Discussionmentioning

confidence: 99%

“… 39 This dual-targeted immunosuppression approach results in homologous immune memory and effective antitumor effects. 39 As a result, we employed an immunotherapy combination along with a nanodelivery method, and the outcomes met our expectations. Our study has certain limitations.…”

Section: Discussionmentioning

confidence: 99%

Regulating Tumor-Associated Macrophage Polarization by Cyclodextrin-Modified PLGA Nanoparticles Loaded with R848 for Treating Colon Cancer

Yuan,

Gui,

Chen

et al. 2024

IJN

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“…In addition, we also evaluated the efficacy of ansofaxine hydrochloride combination with immunotherapy targeting dendritic cells. Our previous studies have shown that HMGN1 [toll-like receptor (TLR) 4 agonist] and 3M-052 (TLR7/ 8 agonist) can work synergistically to stimulate dendritic cell activation (Zhu et al, 2023). HMGN1 and 3M-052 by intratumoral injection (Figure 6A).…”

Section: Combination Therapy With Ansofaxine Hydrochloride Hmgn1 and ...mentioning

confidence: 98%

Ansofaxine hydrochloride inhibits tumor growth and enhances Anti-TNFR2 in murine colon cancer model

Jing,

Wan,

Nie

et al. 2023

Front. Pharmacol.

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Introduction: As psychoneuroimmunology flourishes, there is compelling evidence that depression suppresses the anti-tumor immune response, promotes the progression of cancer, and inhibits the effectiveness of cancer immunotherapy. Recent studies have reported that antidepressants can not only alleviate the depressant condition of cancer patients, but also strengthen the anti-tumor immunity, thus suppressing tumors. Tumor necrosis factor receptor 2 (TNFR2) antagonistic antibodies (Anti-TNFR2) targeting tumor-infiltrating regulatory T cells (Tregs) has achieved great results in preclinical studies, and with a favorable toxicity profile than existing immunotherapies, and is expected to become a new generation of more effective treatment strategies. Understanding the effects of combination therapy with antidepressants and Anti-TNFR2 may help design new strategies for cancer immunotherapy.Methods: We treated CT26, HCT116, MCA38 and SW620 colon cancer cells with fluoxetine (0–50 µM), ansofaxine hydrochloride (0–50 µM) and amitifadine hydrochloride (0–150 µM) to examine their effects on cell proliferation and apoptosis. We explored the antitumor effects of ansofaxine hydrochloride in combination with or without Anti-TNFR in subcutaneously transplanted CT26 cells in tumor-bearing mouse model. Antitumor effects were evaluated by tumor volume. NK cell, M1 macrophage cell, CD4+ T cell, CD8+ T cell, exhausted CD8+ T and regulatory T cell (Tregs) subtypes were measured by flow cytometry. 5-hydroxytryptamine, dopamine and norepinephrine levels were measured by ELISA.Results: Oral antidepression, ansofaxine hydrochloride, enhanced peripheral dopamine levels, promoted CD8+T cell proliferation, promoted intratumoral infiltration of M1 and NK cells, decreased the proportion of tumor-infiltrating exhausted CD8+T cells, and strengthened anti-tumor immunity, thereby inhibiting colon cancer growth. In combination therapy, oral administration of ansofaxine hydrochloride enhanced the efficacy of Anti-TNFR2, and produced long-term tumor control in with syngeneic colorectal tumor-bearing mice, which was attributable to the reduction in tumor-infiltrating Treg quantity and the recovery of CD8+ T cells function.Discussion: In summary, our data reveal the role of ansofaxine hydrochloride in modulating the anti-tumor immunity. Our results support that exhausted CD8+T is an important potential mechanism by which ansofaxine hydrochloride activates anti-tumor immunity and enhances anti-tumor effects of anti-TNFR2.

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Glucocorticoids in lung cancer: Navigating the balance between immunosuppression and therapeutic efficacy

Xu,

Ye,

Cao

et al. 2024

Heliyon

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

Cited by 6 publications

References 38 publications

Regulating Tumor-Associated Macrophage Polarization by Cyclodextrin-Modified PLGA Nanoparticles Loaded with R848 for Treating Colon Cancer

Regulating Tumor-Associated Macrophage Polarization by Cyclodextrin-Modified PLGA Nanoparticles Loaded with R848 for Treating Colon Cancer

Ansofaxine hydrochloride inhibits tumor growth and enhances Anti-TNFR2 in murine colon cancer model

Glucocorticoids in lung cancer: Navigating the balance between immunosuppression and therapeutic efficacy

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