INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 23
·期 18
·10887
·
IF 6.208
Jing Jie,Guomu Liu,Jingyue Feng,Desheng Huo,Yixuan Wu,Hongyan Yuan,Guixiang Tai,Weihua Ni
Our previous study found that CpG oligodeoxynucleotides 1826 (CpG 1826), combined with mucin 1 (MUC1)-maltose-binding protein (MBP) (M-M), had certain antitumor activity. However, this combination is less than ideal for tumor suppression (tumors vary in size and vary widely among individuals), with a drawback being that CpG 1826 is unstable. To solve these problems, here, we evaluate MF59/CpG 1826 as a compound adjuvant with M-M vaccine on immune response, tumor suppression and survival. The results showed that MF59 could promote the CpG 1826/M-M vaccine-induced tumor growth inhibition and a Th1-prone cellular immune response, as well as reduce the individual differences of tumor growth and prolonged prophylactic and therapeutic mouse survival. Further research showed that MF59 promotes the maturation of DCs stimulated by CpG1826/M-M, resulting in Th1 polarization. The possible mechanism is speculated to be that MF59 could significantly prolong the retention time of CpG 1826, or the combination of CpG 1826 and M-M, as well as downregulate IL-6/STAT3 involved in MF59 combined CpG 1826-induced dendritic cell maturation. This study clarifies the utility of MF59/CpG 1826 as a vaccine compound adjuvant, laying the theoretical basis for the development of a novel M-M vaccine.Keywords:MF59;CpG 1826;compound adjuvant;tumor vaccine;MUC1-MBP;dendritic cells
研究领域:
免疫学
·
肿瘤学
·
疫苗学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Ruoxi Yang,Yongxiang Di,Xiaoning Song,Huimin Zhao,Yide Cheng,Cunzhen Lu,Ying Yang,Minjie Sun,Zhanwei Zhou
Cancer immunotherapy suffers from inefficient antigen presentation owing to the limited endocytosis of antigen by dendritic cells (DCs) and dysfunction of DCs in the immunosuppressive tumor microenvironment (ITME). Here, we revealed that cinnamaldehyde-grafted polyethylenimine (PC) held the potential to serve as a neoadjuvant to modulate the above processes and thus potentiate immune responses. The PC neoadjuvant could capture the tumor antigen generated during chemotherapy to enhance the crosstalk between the antigen and DCs. Then, it depleted the intracellular glutathione by the in situ Michael addition reaction, which not only activated the NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) pathway to promote DCs maturation but also triggered the antigen release. As a result, it significantly augmented antigen presentation with a 46% ratio of DCs maturation and a 53% ratio of CD8+ T cell infiltration in low immunogenic murine breast cancer.
研究领域:
肿瘤学
·
免疫学
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Zhicheng Le,Jiang Qian,Haolin Chen,Zepeng He,Runcheng Tan,Hong Liu,Zhenfu Wen,Yi Shi,Zhijia Liu,Yongming Chen
Encouraging results from clinical trials have underscored the potential of gene-pulsed dendritic cell (DC) vaccines as a viable approach for immunotherapy. However, insufficient gene delivery and functional deficiencies in antigen presentation, migratory capacity and cytokine release of DC vaccines limited its broader clinical application. Here, a combinatorial design of cationic gemini amphiphile (GA) molecular library based on the four-component Ugi reaction (Ugi-4CR) has been developed to identify versatile non-viral vectors for gene-engineered DC vaccines. We demonstrated that the leading GA enabled robust transfection of plasmid DNA or mRNA into the DCs through the formation of minimalist binary complexes, which exhibited great advantages of low carrier/gene ratios, high gene loading efficiency and well biocompatibility. The identified GA stimulated strong type I interferon (IFN) expression via the intracellular stimulator of interferon genes (STING) pathway and enhanced DC maturation and activation, which could potentially facilitate strong immunogenicity of DC vaccines. Importantly, DC maturation and activation could be further strengthened by co-delivering maturation stimuli with mRNA/GA complexes, and adoptive transfer of gene-engineered DC vaccines elicited strong T cell responses and thus inhibited tumor growth in vivo . The further studies indicated GAs can be formulated into lipid nanoparticle (LNP)-like quinary complexes that presented 6.9-fold higher mRNA delivery efficiency on the DCs than the commercial Lipofectamine 2000. These results suggest that GA-based molecular library is a powerful platform to develop versatile gene delivery vectors for immune cell engineering.
研究领域:
免疫学
·
分子生物学
·
药学
·
癌症研究
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Zhaoting Li,Yueyang Deng,Honghao Sun,Caixia Tan,Heming Li,Fanyi Mo,Yixin Wang,Jing Li,Zhanwei Zhou,Minjie Sun
Tumor hypoxia and high glutathione (GSH) expression promote regulatory T cell (Treg) infiltration and maintain its immunosuppressive function, which significantly reduces the response rate of cancer immunotherapy . Here, we developed an immunomodulatory nano-formulation ( [email protected] ) to reverse Treg-mediated immunosuppression by redox regulation in the tumor microenvironment (TME). Oxygen carried in perfluorocarbon (PFC) was delivered to the TME, thus relieving the hypoxic condition and inhibiting Treg infiltration. More importantly, GSH depletion by the prodrug efficiently restricted the Foxp3 expression and immunosuppressive function of Tregs, thus breaking the shackles of tumor immunosuppression. Additionally, the supplement of oxygen cooperated with the consumption of GSH to enhance the irradiation-induced immunogenic cell death and subsequent dendritic cell (DC) maturation, thereby efficiently promoting the activation of effector T cells and restricting the immunosuppression of Tregs. Collectively, the [email protected] nano-formulation reverses Treg-mediated immunosuppression and regulates the redox balance in the TME to boost anti-tumor immunity and prolong the survival of tumor-bearing mice, which provides a new immunoregulatory strategy from the perspective of redox modulation.
研究领域:
癌症免疫学
·
纳米技术
·
免疫治疗
·
肿瘤微环境
·
氧化还原生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）