Dual-adjuvant effect of pH-sensitive liposomes loaded with STING and TLR9 agonists regress tumor development by enhancing Th1 immune response

Kocabaş, Banu Bayyurt; Almacioglu, Kubra; Bulut, Esin Alpdundar; Güçlüler, Gözde; Tincer, Gizem; Bayik, Defne; Gürsel, Mayda; Gürsel, İhsan

doi:10.1016/j.jconrel.2020.09.040

Cited by 51 publications

(31 citation statements)

References 41 publications

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“…What’s more, researchers found that CDNs treatment skewed the T cell repertoire toward the Th1 type with increased levels of IFN-γ ( 53 ). Consistent with this result, intra-tumor injection of STING agonist could not only induce strong CD8 + T cells responses but also induce Th1 differentiation or reduce the suppressive Foxp3 + Treg populations to a large extent to exert anti-tumor effects ( 41 , 54 , 55 ). All above results suggested the cGAS-STING pathway, as a cytosolic DNA-sensing pathway, played the potential contribution of anti-tumor efficiency through mediating the recruitment, activation, and differentiation of CD4 + and CD8 + T cells, especially the CD8 + T cells.…”

Section: Cancersupporting

confidence: 74%

The cGAS-STING Pathway: A Promising Immunotherapy Target

Ou¹,

Zhang²,

Cheng³

et al. 2021

Front. Immunol.

103

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With the continuous development of immunotherapy, researchers have paid more attention to the specific immune regulatory mechanisms of various immune responses in different diseases. As a novel and vital innate immune signal pathway, the cGAS-STING signal pathway activated by nucleic acid substances, interplays with other immune responses, by which it participates in regulating cancer, autoimmune and inflammatory diseases, microbial and parasitic infectious diseases, and other diseases. With the exception of its role in innate immunity, the growing list of researches demonstrated expanding roles of the cGAS-STING signal pathway in bridging the innate immunity (macrophage polarization) with the adaptive immunity (T lymphocytes differentiation). Macrophages and T lymphocytes are the most representative cells of innate immunity and adaptive immunity, respectively. Their polarization or differentiation are involved in the pathogenesis and progression of various diseases. Here we mainly summarized recent advanced discoveries of how the cGAS-STING signal pathway regulated macrophages polarization and T lymphocytes differentiation in various diseases and vaccine applications, providing a promising direction for the development and clinical application of immunotherapeutic strategies for related diseases.

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Section: Cancersupporting

confidence: 74%

The cGAS-STING Pathway: A Promising Immunotherapy Target

Ou¹,

Zhang²,

Cheng³

et al. 2021

Front. Immunol.

103

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“…Synergistic modulation of multiple immune signaling pathways of APCs is a promising way to enhance neoantigen cross-presentation. − Accordingly, CpG-oligodeoxynucleotides (CpG-ODN), Toll-like receptor 9 (TLR9) agonists, have shown potent immunostimulatory properties by enhancing cross-presentation of APCs through increasing expression of MHC-II, CD86/80 molecules, and Type I interferon under the existence of antigens to elicit innate immunity. − Moreover, synergistic activation of stimulator of interferon gene (STING) pathway and TLR9 pathway to induce strong Th1-type responses, enhanced IFN-γ production, and cytotoxic CD8+T-cell responses could more efficiently boost cancer immunotherapy. ,− However, the short-term activation of APCs through single bolus injection within 2 days is not enough to provide long durability of immune protection. , Recent works designed injectable PNP-gels to prolong the codelivery of antigen/adjuvant to create a local inflammatory niche for enhancing the magnitude and duration of germinal center responses with a unique kinetics. − Comparably, silk-gel may enact as an ideal vector system for biomedical applications due to its biocompatible and biodegradable properties without immunogenicity and cytotoxicity, and it has been extensively used as a surgical suture and an absorbable surgical mesh in the clinic for a long history. − …”

Section: Resultsmentioning

confidence: 99%

Neoantigen Immunotherapeutic-Gel Combined with TIM-3 Blockade Effectively Restrains Orthotopic Hepatocellular Carcinoma Progression

et al. 2022

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Herein, we integrate the Hepa1–6 liver cancer-specific neoantigen, toll-like receptor 9 agonist and stimulator of interferon genes agonist by silk-hydrogel package, and combine with TIM-3 blockade to elicit robust antitumor immunity for effectively suppressing orthotopic hepatocellular carcinoma (HCC) progression. Unlike intradermal injection of simple mixed components with short-term immune protection, the neoantigen immunotherapeutic-gels evoke long-term immune protection to achieve significant prophylactic and therapeutic activity against HCC through only one-shot administration without any side effects. Notably, the synergized immunotherapy by further combining NGC-gels with TIM-3 antibody significantly reduces regulatory T-cells and increases the IFN-γ and IL-12p70 levels in tumor tissues for promoting the infiltration of IFN-γ+CD8+T-cells and 41BB+CD8+T-cells to achieve complete remission (4/7) and prevent pulmonary metastasis in orthotopic HCC, and establish long-term memory against tumor rechallenge with remarkably longer survival time (180 days). Overall, this study provides an attractive and promising synergistic strategy for HCC immunotherapy with possible clinical translation prospects.

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“…They induce the production of immune regulatory cytokines, activate inflammation, local inflammation and cell recruitment, and induce faster, more extensive and stronger immune response (Park et al, 2018). Kocabas et al (Kocabas et al, 2020) prepared dual-adjuvant liposomes by coencapsulating cGAMP and oligodeoxynucleotides (ODN) containing unmethylated CpG motifs (CpGODN) into sterically stabilized cationic liposomes (SSCLs). The SSCLs promoted the formation of type I and type II interferons, the dual-adjuvant liposomes enhanced the immunostimulatory properties of cGAMP and CpGODN, promoted Th1 immunity, and caused melanoma remission by approximately 70%, and the lipid preparations reversed macrophage polarization to an M1 inflammatory phenotype.…”

Section: Application In Traditional Vaccinesmentioning

confidence: 99%

Application of Nanoparticles in Tumour Targeted Drug Delivery and Vaccine

Yao²,

Yang³

et al. 2022

Front. Nanotechnol.

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Cancer is a major cause of death worldwide, and nearly 1 in 6 deaths each year is caused by cancer. Traditional cancer treatment strategies cannot completely solve cancer recurrence and metastasis. With the development of nanotechnology, the study of nanoparticles (NPs) has gradually become a hotspot of medical research. NPs have various advantages. NPs exploit the enhanced permeability and retention (EPR) of tumour cells to achieve targeted drug delivery and can be retained in tumours long-term. NPs can be used as a powerful design platform for vaccines as well as immunization enhancers. Liposomes, as organic nanomaterials, are widely used in the preparation of nanodrugs and vaccines. Currently, most of the anticancer drugs that have been approved and entered clinical practice are prepared from lipid materials. However, the current clinical conversion rate of NPs is still extremely low, and the transition of NPs from the laboratory to clinical practice is still a substantial challenge. In this paper, we review the in vivo targeted delivery methods, material characteristics of NPs and the application of NPs in vaccine preparation. The application of nanoliposomes is also emphasized. Furthermore, the challenges and limitations of NPs are briefly discussed.

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Dual-adjuvant effect of pH-sensitive liposomes loaded with STING and TLR9 agonists regress tumor development by enhancing Th1 immune response

Cited by 51 publications

References 41 publications

The cGAS-STING Pathway: A Promising Immunotherapy Target

The cGAS-STING Pathway: A Promising Immunotherapy Target

Neoantigen Immunotherapeutic-Gel Combined with TIM-3 Blockade Effectively Restrains Orthotopic Hepatocellular Carcinoma Progression

Application of Nanoparticles in Tumour Targeted Drug Delivery and Vaccine

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