Advances of research of Fc-fusion protein that activate NK cells for tumor immunotherapy

Niu, Yan-Xin; Xu, Zhao‐Xu; Yu, Lifeng; Lu, Yongping; Wang, Yan; Wu, C.; Li, Jianing; Huang, Shaoxiong; Song, Xinyue; Wang, Xinyu; Wang, Jiaqi; Li, Binyu; Guo, Yingrui; Yu, Zhaojin; Zhao, Lin; Yi, Dongxu

doi:10.1016/j.intimp.2022.108783

Cited by 9 publications

(5 citation statements)

References 238 publications

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“…Immune cells such as NK cells and T lymphocytes can specifically recognize tumors and effectively impede their growth [ 33 ]. It has been reported that the proliferation of NK cells can promote a good prognosis for solid tumors [ 34 ]. The treatment with GFG alone or in combination with CTX significantly increased the activities of NK cells and T lymphocytes in the Mod group and CTX group ( p < 0.05).…”

Section: Discussionmentioning

confidence: 99%

Synergistic Antitumor Effect of Grifola frondose Polysaccharide—Protein Complex in Combination with Cyclophosphamide in H22 Tumor-Bearing Mice

Zhao

Liu³

et al. 2023

Molecules

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Hepatocellular carcinoma (HCC) is the most common type of liver malignancy and remains a global health threat. The objective of the current study was to determine whether the combination of a cold-water extracted polysaccharide-protein complex from Grifolia frondosa (GFG) and cyclophosphamide (CTX) could inhibit tumor growth by suppressing the expression of angiogenesis-related proteins in H22 tumor-bearing mice. The results showed that the inhibition rate of GFG combined with CTX on H22 tumors was 65.29%, which was significantly higher than that of GFG treatment alone (24.82%). GFG combined with CTX significantly increased the expression levels of vascular endothelial growth factor, basic fibroblast growth factor, matrix metalloproteinase 2, and matrix metalloproteinase 9. Additionally, thymus index, spleen index, natural killer (NK) cell activity, interferon-γ (IFN-γ), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2) levels increased significantly after GFG treatment, especially after high-doses of GFG combined with CTX treatment (p < 0.05). The thymus index, spleen index, NK cell activity, IFN-γ, IL-1β, TNF-α, and IL-2 levels were 1.90, 1.46, 1.30, 2.13, 1.64, 2.03, and 1.24 times of those treated with CTX alone. Thus, we proposed that GFG can alleviate the side effects of CTX by relieving the immunosuppressive effect, liver/renal injury, and oxidative stress. In conclusion, the combination of GFG and CTX for cancer treatment may be a promising strategy, and GFG is expected to be a potential adjuvant alternative for the treatment of HCC.

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Section: Discussionmentioning

confidence: 99%

Synergistic Antitumor Effect of Grifola frondose Polysaccharide—Protein Complex in Combination with Cyclophosphamide in H22 Tumor-Bearing Mice

Zhao

Liu³

et al. 2023

Molecules

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“…In contrast, NK cells, as innate lymphocytes, are non-antigen-recognition agents and can respond rapidly. It had been reported that the proliferation of NK cells is positively correlated with good prognosis in various solid tumors [ 36 ]. Our data showed that DLP120 administration not only markedly enhanced NK cell viability, but also stimulated lymphocyte proliferation and increased lymphocyte subsets ratios.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of the Polysaccharides from Taraxacum mongolicum Leaf by Modulating the p53 Signaling Pathway in H22 Tumor-Bearing Mice

Chen

Yan

et al. 2022

Foods

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Dandelion is an edible plant with a variety of bioactive components. This paper mainly reports the antitumor activity of dandelion polysaccharide DLP120 on H22 tumor-bearing mice. DLP120 is an acidic polysaccharide composed of pectin and arabinogalactan. The results indicate that DLP120 markedly inhibited tumor growth in a dose-dependent manner and attenuated and regulated negative effects on organs. In addition, DLP120 not only increased the viability of spleen lymphocytes and natural killer (NK) cells, but also increased the proportion of lymphocyte subsets in peripheral blood. Furthermore, Hematoxylin-Eosin (HE) staining showed that tumor tissues and cells exhibited typical pathology features. Annexin V FITC/PI staining and cell cycle distribution results further confirmed apoptosis and cell cycle arrest in S and G2 phases. Notably, there was a significant accumulation of reactive oxygen species. Western blotting results demonstrated that the expression of p53 was up-regulated in the DLP120 group. Moreover, the pro-apoptotic protein Bax was up-regulated while the inhibitory-apoptotic protein Bcl-2 was down-regulated. In addition, the expression of Fas and FasL, associated with the death receptor pathway, were also up-regulated. Overall, administration of DLP120 in H22 tumor-bearing mice can not only enhance immunity but also directly induce tumor cell apoptosis.

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“…Fc-fusion protein is the fusion of Fc region of antibody with functional protein or peptide by engineering gene technology, which represents a novel kind of recombinant protein and is a promising biopharmaceutical product in major diseases [18]. They retain the bioactivity of the functional molecules and partial properties of Fc.…”

Section: Introductionmentioning

confidence: 99%

Chimerism of avian IgY‐scFv and truncated IgG‐Fc: A novel strategy in cross‐species antibody generation and enhancement

Ge,

Dias,

Zhang

2024

Immunology

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Chicken single‐chain fragment variable (IgY‐scFv) is a functional fragment and an emerging development in genetically engineered antibodies with a wide range of biomedical applications. However, scFvs have considerably shorter serum half‐life due to the absence of antibody Fc region compared with the full‐length antibody, and usually requires continuous intravenous administration for efficacy. A promising approach to overcome this limitation is to fuse scFv with immunoglobulin G (IgG) Fc region, for better recognition and mediation by the neonatal Fc receptor (FcRn) in the host. In this study, engineered mammalian ΔFc domains (CH2, CH3, and intact Fc region) were fused with anti‐canine parvovirus‐like particles avian IgY‐scFv to produce chimeric antibodies and expressed in the HEK293 cell expression system. The obtained scFv‐CH2, scFv‐CH3, and scFv‐Fc can bind with antigen specifically and dose‐dependently. Surface plasmon resonance investigation confirmed that scFv‐CH2, scFv‐CH3, and scFv‐Fc had different degrees of binding to FcRn, with scFv‐Fc showing the highest affinity. scFv‐Fc had a significantly longer half‐life in mice compared with the unfused scFv. The identified ΔFcs are promising for the development of engineered Fc‐based therapeutic antibodies and proteins with longer half‐lives. The avian IgY‐scFv‐mammalian IgG Fc region opens up new avenues for antibody engineering, and it is a novel strategy to enhance the rapid development and screening of functional antibodies in veterinary and human medicine.

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Advances of research of Fc-fusion protein that activate NK cells for tumor immunotherapy

Cited by 9 publications

References 238 publications

Synergistic Antitumor Effect of Grifola frondose Polysaccharide—Protein Complex in Combination with Cyclophosphamide in H22 Tumor-Bearing Mice

Synergistic Antitumor Effect of Grifola frondose Polysaccharide—Protein Complex in Combination with Cyclophosphamide in H22 Tumor-Bearing Mice

Protective Effect of the Polysaccharides from Taraxacum mongolicum Leaf by Modulating the p53 Signaling Pathway in H22 Tumor-Bearing Mice

Chimerism of avian IgY‐scFv and truncated IgG‐Fc: A novel strategy in cross‐species antibody generation and enhancement

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