Single-component lipid nanoparticles for engineering SOCS1 gene-silenced dendritic cells to boost tumor immunotherapy

Yu, Zexuan; Wu, Mengtong; Huang, Yingshuang; Wang, Yishu; Chen, Yijun; Long, Qiulin; Lin, Ziming; Xue, Lingjing; Ju, Caoyun; Zhang, Can

doi:10.1039/d2bm01549h

Cited by 5 publications

(3 citation statements)

References 33 publications

(44 reference statements)

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“…DCs are the most common and typical APCs in the immune system, 51–54 and the antigen presentation and maturation of APCs is important in the activation of immune responses. 55 Thus, we analyzed the expression of biomarkers expressed on DCs after QS-21/Cryo cell and QS-21/UV-Cryo cell stimulation. According to Fig.…”

Section: Resultsmentioning

confidence: 99%

Immunogenic dead cells engineered by the sequential treatment of ultraviolet irradiation/cryo-shocking for lung-targeting delivery and tumor vaccination

Zang,

Zhang,

Mei

et al. 2024

Biomater. Sci.

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Section: Resultsmentioning

confidence: 99%

Immunogenic dead cells engineered by the sequential treatment of ultraviolet irradiation/cryo-shocking for lung-targeting delivery and tumor vaccination

Zang,

Zhang,

Mei

et al. 2024

Biomater. Sci.

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“…To accomplish desired therapeutic effects, efficient delivery of siRNA into cells is a prerequisite [31]. In this study, we chose OA2, a demonstrated effective cationic lipid nanoparticle with high transfection efficiency [32], as the carrier to deliver the siRNA against RAPSYN gene, which has shown excellent RAPSYN gene silencing in Ph + leukemia cell lines. In addition, OA2-siRAPSYN could significantly inhibit the proliferation of Ph + leukemia cell lines, through the regulation of Wnt/β-catenin/c-Myc signaling pathway, which is another advantage to possibly eliminate leukemia stem cells in Ph + leukemia patients [33][34][35].…”

Section: Discussionmentioning

confidence: 99%

Targeted degradation of oncogenic BCR-ABL by silencing the gene of NEDD8 E3 ligase RAPSYN

Sun,

Wang,

Liu

et al. 2024

J Nanobiotechnol

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Tyrosine kinase inhibitors have been the standard treatment for patients with Philadelphia chromosome-positive (Ph+) leukemia. However, a series of issues, including drug resistance, relapse and intolerance, are still an unmet medical need. Here, we report the targeted siRNA-based lipid nanoparticles in Ph+ leukemic cell lines for gene therapy of Ph+ leukemia, which specifically targets a recently identified NEDD8 E3 ligase RAPSYN in Ph+ leukemic cells to disrupt the neddylation of oncogenic BCR-ABL. To achieve the specificity for Ph+ leukemia therapy, a single-chain fragment variable region (scFv) of anti-CD79B monoclonal antibody was covalently conjugated on the surface of OA2-siRAPSYN lipid nanoparticles to generate the targeted lipid nanoparticles (scFv-OA2-siRAPSYN). Through effectively silencing RAPSYN gene in leukemic cell lines by the nanoparticles, BCR-ABL was remarkably degraded accompanied by the inhibition of proliferation and the promotion of apoptosis. The specific targeting, therapeutic effects and systemic safety were further evaluated and demonstrated in cell line-derived mouse models. The present study has not only addressed the clinical need of Ph+ leukemia, but also enabled gene therapy against a less druggable target. Graphical Abstract

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“…One interesting example of modulating SOCS1 levels, is the lipid nanoparticle (LNP) delivery of SOCS1-targeting small interfering RNA (siRNA) to bone marrow-derived DCs. Vaccination with OVA-specific DCs containing Socs1 siRNA prior to challenge with OVA-bearing B16F10 melanoma cells, successfully suppressed tumor growth through increased cytokine secretion and antigen presentation ( 182 ).…”

Section: Discussionmentioning

confidence: 99%

SOCS1 is a critical checkpoint in immune homeostasis, inflammation and tumor immunity

Bidgood,

Keating,

Doggett

et al. 2024

Front. Immunol.

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The Suppressor of Cytokine Signaling (SOCS) family proteins are important negative regulators of cytokine signaling. SOCS1 is the prototypical member of the SOCS family and functions in a classic negative-feedback loop to inhibit signaling in response to interferon, interleukin-12 and interleukin-2 family cytokines. These cytokines have a critical role in orchestrating our immune defence against viral pathogens and cancer. The ability of SOCS1 to limit cytokine signaling positions it as an important immune checkpoint, as evidenced by the detection of detrimental SOCS1 variants in patients with cytokine-driven inflammatory and autoimmune disease. SOCS1 has also emerged as a key checkpoint that restricts anti-tumor immunity, playing both a tumor intrinsic role and impacting the ability of various immune cells to mount an effective anti-tumor response. In this review, we describe the mechanism of SOCS1 action, focusing on the role of SOCS1 in autoimmunity and cancer, and discuss the potential for new SOCS1-directed cancer therapies that could be used to enhance adoptive immunotherapy and immune checkpoint blockade.

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Single-component lipid nanoparticles for engineering SOCS1 gene-silenced dendritic cells to boost tumor immunotherapy

Abstract: Dendritic cells (DCs) that can prime antitumor responses indicate a great potential in tumor immunotherapy, whereas the unsatisfactory effect which can be ascribed in part to the high expressions of...

Cited by 5 publications

References 33 publications

Immunogenic dead cells engineered by the sequential treatment of ultraviolet irradiation/cryo-shocking for lung-targeting delivery and tumor vaccination

Immunogenic dead cells engineered by the sequential treatment of ultraviolet irradiation/cryo-shocking for lung-targeting delivery and tumor vaccination

Targeted degradation of oncogenic BCR-ABL by silencing the gene of NEDD8 E3 ligase RAPSYN

SOCS1 is a critical checkpoint in immune homeostasis, inflammation and tumor immunity

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