Enhancement of Immune Checkpoint Inhibitor-Mediated Anti-Cancer Immunity by Intranasal Treatment of Ecklonia cava Fucoidan against Metastatic Lung Cancer

Zhang, Wei; Hwang, Juyoung; Yadav, Dhananjay; An, Eun‐Koung; Kwak, Minseok; Lee, Peter Chang-Whan

doi:10.3390/ijms22179125

Cited by 24 publications

(17 citation statements)

References 60 publications

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“…Fucoidan extracted from three species of algae, among them Fucus vesiculosus , promoted proliferation and activity of ex vivo PBMCs and potentiated anti-PD-1 effects [ 68 ]. Intranasal administration of Ecklonia-cava -extracted fucoidan enhanced anti-PD-L1 mediated anti-cancer activities against melanoma and carcinoma tumor growth in lungs [ 69 ]. Fucoidan of Luminaria japonica enhanced anticancer efficacy of anti-PD-L1 antibodies against Lewis lung carcinoma [ 70 ].…”

Section: Discussionmentioning

confidence: 99%

Anti-Proliferative and Pro-Apoptotic vLMW Fucoidan Formulas Decrease PD-L1 Surface Expression in EBV Latency III and DLBCL Tumoral B-Cells by Decreasing Actin Network

et al. 2023

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Epstein–Barr virus (EBV) infects 95% of the world’s population and persists latently in the body. It immortalizes B-cells and is associated with lymphomas. LCLs (lymphoblastoid cell lines, EBV latency III B-cells) inhibit anti-tumoral T-cell response following PD-L1 overexpression (programmed death-ligand 1 immune checkpoint). Many cancer cells, including some DLBCLs (diffuse large B-cell lymphomas), also overexpress PD-L1. Immunotherapies are based on inhibition of PD-L1/PD-1 interactions but present some dose-dependent toxicities. We aim to find new strategies to improve their efficiency by decreasing PD-L1 expression. Fucoidan, a polysaccharide extracted from brown seaweed, exhibits immunomodulatory and anti-tumor activities depending on its polymerization degree, but data are scarce on lymphoma cells or immune checkpoints. LCLs and DLBCLs cells were treated with native fucoidan (Fucus vesiculosus) or original very-low-molecular-weight fucoidan formulas (vLMW-F). We observed cell proliferation decrease and apoptosis induction increase with vLMW-F and no toxicity on normal B- and T-cells. We highlighted a decrease in transcriptional and PD-L1 surface expression, even more efficient for vLMW than native fucoidan. This can be explained by actin network alteration, suggesting lower fusion of secretory vesicles carrying PD-L1 with the plasma membrane. We propose vLMW-F as potential adjuvants to immunotherapy due to their anti-proliferative and proapoptotic effects and ability to decrease PD-L1 membrane expression.

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Section: Discussionmentioning

confidence: 99%

Anti-Proliferative and Pro-Apoptotic vLMW Fucoidan Formulas Decrease PD-L1 Surface Expression in EBV Latency III and DLBCL Tumoral B-Cells by Decreasing Actin Network

et al. 2023

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“…Among these was the fucoidan from Ecklonia cava (ECF), administered intranasally in mice, which promoted the activation of dendritic cells, natural killer cells (NK) and T cells. In addition, it was found that intranasal injection of ECF enhanced the antitumor effect of PD-L1 antibodies on melanoma B16 and carcinoma CT-26 in lung metastases, showing that ECF could function as an adjuvant enhancing the immunotherapeutic effect of immune checkpoint inhibitors against metastatic lung cancer [ 25 ].…”

Section: Antitumor Activitymentioning

confidence: 99%

Perspectives for the Use of Fucoidans in Clinical Oncology

Kiselevskiy

Anisimova

Ustyuzhanina

et al. 2022

IJMS

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Fucoidans are natural sulfated polysaccharides that have a wide range of biological functions and are regarded as promising antitumor agents. The activity of various fucoidans and their derivatives has been demonstrated in vitro on tumor cells of different histogenesis and in experiments on mice with grafted tumors. However, these experimental models showed low levels of antitumor activity and clinical trials did not prove that this class of compounds could serve as antitumor drugs. Nevertheless, the anti-inflammatory, antiangiogenic, immunostimulating, and anticoagulant properties of fucoidans, as well as their ability to stimulate hematopoiesis during cytostatic-based antitumor therapy, suggest that effective fucoidan-based drugs could be designed for the supportive care and symptomatic therapy of cancer patients. The use of fucoidans in cancer patients after chemotherapy and radiation therapy might promote the rapid improvement of hematopoiesis, while their anti-inflammatory, immunomodulatory, and anticoagulant effects have the potential to improve the quality of life of patients with advanced cancer.

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“…The alga Ecklonia cava is an edible medicinal food that is widely consumed in Korea and Japan for its reported multiple health benefits that include anti-cancer [ 7 ], anti-diabetes [ 8 ], anti-inflammatory [ 9 ], and anti-obesity [ 10 ] properties. These studies from two publications suggest that the alga and isolated bioactive compounds might be safe for human consumption.…”

Section: Introductionmentioning

confidence: 99%

Edible algae (Ecklonia cava) bioprocessed with mycelia of shiitake (Lentinula edodes) mushrooms in liquid culture and its isolated fractions protect mice against allergic asthma

Lee

Jang²,

Hwang³

et al. 2022

BMC Complement Med Ther

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Background Ecklonia cava is an edible marine brown alga harvested from the ocean that is widely consumed in Asian countries as a health-promoting medicinal food The objective of the present study is to evaluate the anti-asthma mechanism of a new functional food produced by bioprocessing edible algae Ecklonia cava and shiitake Lentinula edodes mushroom mycelia and isolated fractions. Methods We used as series of methods, including high performance liquid chromatography, gas chromatography, cell assays, and an in vivo mouse assay to evaluate the asthma-inhibitory effect of Ecklonia cava bioprocessed (fermented) with Lentinula edodes shiitake mushroom mycelium and its isolated fractions in mast cells and in orally fed mice. Results The treatments inhibited the degranulation of RBL-2H3 cells and immunoglobulin E (IgE) production, suggesting anti-asthma effects in vitro. The in vitro anti-asthma effects in cells were confirmed in mice following the induction of asthma by alumina and chicken egg ovalbumin (OVA). Oral administration of the bioprocessed Ecklonia cava and purified fractions suppressed the induction of asthma and was accompanied by the inhibition of inflammation- and immune-related substances, including eotaxin; thymic stromal lymphopoietin (TSLP); OVA-specific IgE; leukotriene C 4 (LTC4); prostaglandin D2 (PGD 2 ); and vascular cell adhesion molecule-1 (VCAM-1) in bronchoalveolar lavage fluid (BALF) and other fluids and organs. Th2 cytokines were reduced and Th1 cytokines were restored in serum, suggesting the asthma-induced inhibitory effect is regulated by the balance of the Th1/Th2 immune response. Serum levels of IL-10, a regulatory T cell (Treg) cytokine, were increased, further favoring reduced inflammation. Histology of lung tissues revealed that the treatment also reversed the thickening of the airway wall and the contraction and infiltration of bronchial and blood vessels and perialveolar inflammatory cells. The bioprocessed Ecklonia cava/mushroom mycelia new functional food showed the highest inhibition as compared with commercial algae and the fractions isolated from the bioprocessed product. Conclusions The in vitro cell and in vivo mouse assays demonstrate the potential value of the new bioprocessed formulation as an anti-inflammatory and anti-allergic combination of natural compounds against allergic asthma and might also ameliorate allergic manifestations of foods, drugs, and viral infections.

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Enhancement of Immune Checkpoint Inhibitor-Mediated Anti-Cancer Immunity by Intranasal Treatment of Ecklonia cava Fucoidan against Metastatic Lung Cancer

Cited by 24 publications

References 60 publications

Anti-Proliferative and Pro-Apoptotic vLMW Fucoidan Formulas Decrease PD-L1 Surface Expression in EBV Latency III and DLBCL Tumoral B-Cells by Decreasing Actin Network

Anti-Proliferative and Pro-Apoptotic vLMW Fucoidan Formulas Decrease PD-L1 Surface Expression in EBV Latency III and DLBCL Tumoral B-Cells by Decreasing Actin Network

Perspectives for the Use of Fucoidans in Clinical Oncology

Edible algae (Ecklonia cava) bioprocessed with mycelia of shiitake (Lentinula edodes) mushrooms in liquid culture and its isolated fractions protect mice against allergic asthma

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