RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:SOLVx therapeutics vaccine - Activate T-cell immunity using broad surveillance epitope strategy against mutant strains SARS-COV2.
SOLVx therapeutics vaccine - Activate T-cell immunity using broad surveillance epitope strategy against mutant strains SARS-COV2.
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高度易变的新型冠状病毒持续重塑其基因组,使预防性疫苗失效。本研究旨在验证 SOLVx 治疗性疫苗的抗病毒效果和安全性。肽由 Neo7Logix 研发设计,并由 Genescript GLP 实验室合成,纯度为 95%。研究使用 BALB/C 小鼠建立 HCoV-229E 突变冠状病毒模型,并通过 qPCR 检测肺组织病毒 mRNA。处死小鼠后,使用相应生物样本评估治疗对多项指标的影响,包括肺部病毒 mRNA、细胞因子水平、PBMC 分化以及血液学和生化指标。流式细胞术免疫分型显示,SOLVx(系列 1)处理小鼠的 T 细胞亚群、B 细胞比例和 NK 细胞群体均呈剂量依赖性显著增加。血清免疫球蛋白 G 和 M 水平显著升高(P<0.001)。肽治疗组的 IL-6、IL-10 和 TNF-α 水平随剂量增加而显著下降(P<0.001),IFN-γ 水平则显著升高(P<0.001)。
总之,qPCR 结果提示 SOLVx 疫苗(系列 1)可剂量依赖性降低 SARS-CoV-2 病毒感染性。SOLVx 的体液、细胞和功能活性显示,该疫苗通过多种机制靶向病毒演化,提供免疫应答和防御并清除 SARS-CoV-2。
Highly mutable Coronavirus-19 continuously reconstructs its genome and renders prophylactic vaccines ineffective. The objective of the present study was to demonstrate the anti-viral efficacy and safety of the SOLVx therapeutics vaccine. The peptides were designed with Neo7Logix R&D and synthesized with Genescript GLP laboratory with 95 % purity. BALB/C mice were used to develop the HCoV-229E mutant coronavirus model and viral mRNA confirmation in the lung tissue was assessed with qPCR.
Mice were euthanized and effects of treatment on various parameters (Viral mRNA in lungs, cytokine levels, PBMC differentiation, hematological and biochemical) were assessed with respective biological samples. Immuno-typing analysis of PBMCs by flowcytometry showed marked increase in T cell subsets, % of B cells and NK cell population in mice treated with SOLVx (Series 1) in a dose dependent manner.
Serum immunoglobulin G, and M levels were increased significantly (P < 0. 001). In the peptide treatment groups, there was a dose dependent statistically significant decrease in IL-6, IL-10 and TNF- levels (P < 0. 001). IFN- was elevated in treatment group significantly (P < 0. 001).
In conclusion, the qPCR results suggested that the SOLVx vaccine (Series 1) reduced the SARS-COV2 virus infectivity in a dose dependent manner. The humoral, cellular and functional activity of the SOLVx showed that it worked through multi-mechanistic targeting the virus evolution, offering immune response, defense and eradication of the SARS-COV2 virus.
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