Dataset Information

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

ABSTRACT: Although fucoidan, a well-studied seaweed-extracted polysaccharide, has shown immune stimulatory effects that elicit anticancer immunity, mucosal adjuvant effects via intranasal administration have not been studied. In this study, the effect of Ecklonia cava-extracted fucoidan (ECF) on the induction of anti-cancer immunity in the lung was examined by intranasal administration. In C57BL/6 and BALB/c mice, intranasal administration of ECF promoted the activation of dendritic cells (DCs), natural killer (NK) cells, and T cells in the mediastinal lymph node (mLN). The ECF-induced NK and T cell activation was mediated by DCs. In addition, intranasal injection with ECF enhanced the anti-PD-L1 antibody-mediated anti-cancer activities against B16 melanoma and CT-26 carcinoma tumor growth in the lungs, which were required cytotoxic T lymphocytes and NK cells. Thus, these data demonstrated that ECF functioned as a mucosal adjuvant that enhanced the immunotherapeutic effect of immune checkpoint inhibitors against metastatic lung cancer.

SUBMITTER: Zhang W

PROVIDER: S-EPMC8431244 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Enhancement of Immune Checkpoint Inhibitor-Mediated Anti-Cancer Immunity by Intranasal Treatment of <i>Ecklonia cava</i> Fucoidan against Metastatic Lung Cancer.

Zhang Wei W Hwang Juyoung J Yadav Dhananjay D An Eun-Koung EK Kwak Minseok M Lee Peter Chang-Whan PC Jin Jun-O JO

International journal of molecular sciences 20210824 17

Although fucoidan, a well-studied seaweed-extracted polysaccharide, has shown immune stimulatory effects that elicit anticancer immunity, mucosal adjuvant effects via intranasal administration have not been studied. In this study, the effect of <i>Ecklonia cava</i>-extracted fucoidan (ECF) on the induction of anti-cancer immunity in the lung was examined by intranasal administration. In C57BL/6 and BALB/c mice, intranasal administration of ECF promoted the activation of dendritic cells (DCs), na ...[more]

PMID: 34502035

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Project description:Despite lengthening survival, death rates from metastatic colorectal cancer (CRC) remain unacceptably high, with a bright spot being the demonstration of durable responses in patients with CRC who have mismatch repair-deficient (dMMR) and/or microsatellite instability-high (MSI-H) tumors and are treated with immune checkpoint inhibitor therapy. Nivolumab and pembrolizumab, as well as nivolumab in combination with low-dose ipilimumab-all checkpoint inhibitors-are currently approved by the U.S. Food and Drug Administration (FDA) for patients with MSI-H/dMMR metastatic CRC that progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. Nonetheless, there are a number of questions and considerations in the use of these checkpoint inhibitor therapies. Using a question-and-answer format, this review summarizes the scientific rationale for immune checkpoint inhibitor therapy in CRC, including the effects of tumor factors such as genetic aberrations and mutational load on the immune response, particularly in patients with MSI-H/dMMR disease. We discuss response patterns, response criteria, and immune-related adverse events using findings from published efficacy and safety data of immune checkpoint inhibitor therapy in metastatic CRC. We also discuss issues surrounding treatment sequencing, incorporating approved checkpoint inhibitors into the current treatment paradigm, and the multiple investigational strategies that may optimize immunotherapy for advanced CRC in the future, including novel combination therapies. IMPLICATIONS FOR PRACTICE: Colorectal cancer (CRC) is the third most common cancer in the U.S. Despite advances in chemotherapy, survival remains poor for patients with metastatic CRC. Certain immunotherapy agents have demonstrated long-lasting responses in previously treated patients with immune-responsive microsatellite instability-high/mismatch repair-deficient metastatic CRC, leading to U.S. Food and Drug Administration approval of the immune checkpoint inhibitors nivolumab (with or without low-dose ipilimumab) and pembrolizumab in this population. Combination therapy (e.g., nivolumab with low-dose ipilimumab) has demonstrated numerically higher response rates and improved long-term clinical benefit relative to anti-programmed death-1 monotherapy. Ongoing trials are evaluating immunotherapy in the broader CRC population and novel combinations to optimize immunotherapy for advanced CRC.

Dataset Information

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

Publications

Enhancement of Immune Checkpoint Inhibitor-Mediated Anti-Cancer Immunity by Intranasal Treatment of <i>Ecklonia cava</i> Fucoidan against Metastatic Lung Cancer.

Similar Datasets

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