Astragalus membranaceus–Derived Anti-Programmed Death-1 Monoclonal Antibodies with Immunomodulatory Therapeutic Effects against Tumors

Chang, Fu Ling; Tsai, Keng‐Chang; Lin, Tung‐Ching; Yang, Tien-Wei; Lo, Yan Ni; Chen, Wang Chuan; Chang, Juu En; Lu, Mei-Kuang; Chiou, Chun Tang; Chen, Po Hung; Yen, Yun; Pan, Shiow Lin; Lee, Yu Ching

doi:10.1155/2020/3415471

Cited by 13 publications

(15 citation statements)

References 27 publications

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“…Cosignalling receptors, including costimulatory and coinhibitory receptors, play an indispensable role in regulating the immune response [ 5 ]. Coinhibitory receptors, such as programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte associated-4 (CTLA-4), have been reported to correlate with Treg dysfunction and participate in evading immune surveillance [ 6 – 8 ]. Conversely, costimulatory receptors such as CD28, OX40, and 4-1BB have also been widely implicated in T cell stimulation and immune homeostasis [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Characteristic of TIGIT and DNAM-1 Expression on Foxp3+ γδ T Cells in AML Patients

Jin

Lan

et al. 2020

BioMed Research International

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Foxp3+ γδ regulatory T (γδ Treg) cells promote tumor growth by various mechanisms and induce immuno-senescence. The novel immune checkpoint coinhibitory receptor T cell Ig and ITIM domain (TIGIT) shares similar ligands as the costimulatory receptor DNAX accessory molecule 1 (DNAM-1) and suppresses T cell responses in tumor patients. This study is aimed at characterizing whether the TIGIT/DNAM-1 axis is involved in the distribution and expression of Foxp3+ γδ Treg cell subsets in acute myeloid leukemia (AML) patients of different clinical statuses: de novo AML (27 patients), AML in nonremission (NR) (7 patients), and AML in complete remission (CR) (12 patients). Our data demonstrated that the proportions of Foxp3+, TIGIT+Foxp3+, and DNAM-1+Foxp3+ γδ T cells are significantly higher in de novo and NR patients. High levels of TIGIT and DNAM-1 on Foxp3+ γδ T cells correlated with increased Foxp3+ γδ T cell frequencies. In addition, a high TIGIT/DNAM-1 ratio was observed in de novo AML patients and healthy individuals (HIs). Furthermore, the phenotypic abnormalities in Foxp3+, TIGIT+Foxp3+, and DNAM-1+Foxp3+ γδ T cells were restored when the patients achieved CR after chemotherapy. Moreover, higher TIGIT+Foxp3+ γδ T cells were associated with AML patients who had poor overall survival and were an independent risk factor for prognosis. In conclusion, our study reveals for the first time that the TIGIT/DNAM-1 axis may be involved in Foxp3+ γδ Treg cells and indicates the clinical progression and prognosis of AML patients of different clinical statuses, which is considered beneficial for efficient AML immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Characteristic of TIGIT and DNAM-1 Expression on Foxp3+ γδ T Cells in AML Patients

Jin

Lan

et al. 2020

BioMed Research International

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“…In China, herbal medicine is frequently combined with other treatments to reduce adverse effects (11,12), improve patient quality-of-life, and prolong survival. Many natural products that originate from Chinese herbal medicine exhibit anticancer activities (13)(14)(15), including antiproliferative, pro-apoptotic, antimetastatic, and anti-angiogenic effects. These products have been shown to regulate autophagy, reverse multidrug resistance, balance immunity, and enhance chemotherapy in vitro and in vivo (16).…”

Section: Discussionmentioning

confidence: 99%

Analysis of chemical consistency and the anti-tumor activity of Huangqi-Ezhu (HQ-EZ) concentrated-granules and decoction

Wang¹,

Dou²,

Zhao³

et al. 2020

Ann Palliat Med

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Background: Traditional Chinese medicine decoction and modern concentrated-granules are two kinds of Chinese herbal medicine forms used in clinic at present. The former is extracted by traditional boiling method of a pre-mixed multi-herbal medicine according to the doctor's prescription. The latter is a mixture of extract active ingredients from a single variety of herbs by modern technology. It is not clear whether there is a difference in the content and efficacy of the active components between the two methods. Methods:The effective components of Huangqi-Ezhu (HQ-EZ) traditional decoction and concentratedgranules were determined by HPLC, and the subcutaneous transplanted tumor model of tumor-bearing mice was established to compare the anti-tumor effect. HQ-EZ traditional decoction and concentrated-granules were given respectively by continuous intragastric administration for 15 days. After the last administration the tumor tissue, liver and kidney were removed completely, and the corresponding indexes were detected.Results: Active components of concentrated-granules and traditional decoction are basically the same.Both of TCM forms have great anti-tumor effect against lung cancer, without toxify to liver and kidney. Conclusions:The two preparation methods have their own advantages in effective components, and the compatibility of HQ-EZ can inhibit the tumor growth of tumor-bearing mice, and has no liver and kidney toxicity.

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“…In recent years, with the rise of immune agents, the immunomodulatory function of traditional Chinese medicine on immune checkpoints has also aroused great interest. Previous studies (Chang F.-L. et al, 2020) have shown that APS can significantly inhibit the growth of melanoma cells in transgenic mice and reduce the expression of PD-L1 in tumors, suggesting that the anti-tumor immunosuppressive mechanism of APS may also be related to the regulation of PD-1/PD-L1 signal pathway. A study demonstrated that there was no significant difference in tumor inhibition compared with anti-PD-1 combined with ixabepilone or APS, indicating that APS can maintain an effective dose of anti-PD-1 antibody in vivo, and delay the progression of tumor or tumorigenesis by increasing the activity of T cells, which may improve the synergistic effect (Chang F.-L. et al, 2020).…”

Section: Astragalus Polysaccharidesmentioning

confidence: 97%

“…Previous studies (Chang F.-L. et al, 2020) have shown that APS can significantly inhibit the growth of melanoma cells in transgenic mice and reduce the expression of PD-L1 in tumors, suggesting that the anti-tumor immunosuppressive mechanism of APS may also be related to the regulation of PD-1/PD-L1 signal pathway. A study demonstrated that there was no significant difference in tumor inhibition compared with anti-PD-1 combined with ixabepilone or APS, indicating that APS can maintain an effective dose of anti-PD-1 antibody in vivo, and delay the progression of tumor or tumorigenesis by increasing the activity of T cells, which may improve the synergistic effect (Chang F.-L. et al, 2020). In addition, another research showed that APS enhances the chemotherapy by stimulating host immunity through reducing the PD-L1 expression of tumor surface (Chang H.-L. et al, 2020).…”

Section: Astragalus Polysaccharidesmentioning

confidence: 97%

“…Astragali Radix (Huangqi in Chinese), the dried root of Astragalus membranaceus, a commonly used Chinese medicine, has been proven to be effective in enhancing the immune system and treating pathological diseases, even cancer (Chang F.-L. et al, 2020). The astragalus polysaccharide (APS) is the main active component of A. membranaceus extract, and the combined treatment strategy used with other drugs (such as cancer chemotherapy and immunosuppressants drugs) has also been proved to obviously reduce the toxicity of these drugs and enhance the therapeutic effect (Li et al, 2020).…”

Section: Astragalus Polysaccharidesmentioning

confidence: 99%

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Natural Polysaccharides and Their Derivates: A Promising Natural Adjuvant for Tumor Immunotherapy

Wang

et al. 2021

Front. Pharmacol.

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The treatment process of tumor is advanced with the development of immunotherapy. In clinical experience, immunotherapy has achieved very significant results. However, the application of immunotherapy is limited by a variety of immune microenvironment. For a long time in the past, polysaccharides such as lentinan and Ganoderma lucidum glycopeptide have been used in clinic as adjuvant drugs to widely improve the immunity of the body. However, their mechanism in tumor immunotherapy has not been deeply discussed. Studies have shown that natural polysaccharides can stimulate innate immunity by activating upstream immune cells so as to regulate adaptive immune pathways such as T cells and improve the effect of immunotherapy, suggesting that polysaccharides also have a promising future in cancer therapy. This review systematically discusses that polysaccharides can directly or indirectly activate macrophages, dendritic cells, natural killer cells etc., binding to their surface receptors, inducing PI3K/Akt, mitogen-activated protein kinase, Notch and other pathways, promote their proliferation and differentiation, increasing the secretion of cytokines, and improve the state of immune suppression. These results provide relevant basis for guiding polysaccharide to be used as adjuvants of cancer immunotherapy.

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Astragalus membranaceus–Derived Anti-Programmed Death-1 Monoclonal Antibodies with Immunomodulatory Therapeutic Effects against Tumors

Cited by 13 publications

References 27 publications

Characteristic of TIGIT and DNAM-1 Expression on Foxp3+ γδ T Cells in AML Patients

Characteristic of TIGIT and DNAM-1 Expression on Foxp3+ γδ T Cells in AML Patients

Analysis of chemical consistency and the anti-tumor activity of Huangqi-Ezhu (HQ-EZ) concentrated-granules and decoction

Natural Polysaccharides and Their Derivates: A Promising Natural Adjuvant for Tumor Immunotherapy

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