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1.
Clin Infect Dis ; 74(1): 144-148, 2022 01 07.
Article in English | MEDLINE | ID: covidwho-1621566

ABSTRACT

We are learning that the host response to severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2) infection is complex and highly dynamic. Effective initial host defense in the lung is associated with mild symptoms and disease resolution. Viral evasion of the immune response can lead to refractory alveolar damage, ineffective lung repair mechanisms, and systemic inflammation with associated organ dysfunction. The immune response in these patients is highly variable and can include moderate to severe systemic inflammation and/or marked systemic immune suppression. There is unlikely to be a "one size fits all" approach to immunomodulation in patients with coronavirus disease 2019 (COVID-19). We believe that a personalized, immunophenotype-driven approach to immunomodulation that may include anticytokine therapy in carefully selected patients and immunostimulatory therapies in others is the shortest path to success in the study and treatment of patients with critical illness due to COVID-19.


Subject(s)
COVID-19 , Immunomodulation , Precision Medicine , COVID-19/immunology , COVID-19/therapy , Cytokines , Humans , Immunity , Lung , SARS-CoV-2
2.
Immunotherapy ; 13(12): 1011-1029, 2021 08.
Article in English | MEDLINE | ID: covidwho-1362211

ABSTRACT

The use of immune checkpoint inhibitors in patients with metastatic melanoma generates clinical benefit, including improved survival. Yet disease resistance and immune-related adverse events persist as unmet needs. Sargramostim, a yeast-derived recombinant human GM-CSF, has shown clinical activity against diverse solid tumors, including metastatic melanoma. Here we review the use of sargramostim for treatment of advanced melanoma. Potential sargramostim applications in melanoma draw on the unique ability of GM-CSF to link innate and adaptive immune responses. We review preclinical and translational data describing the mechanism of action of sargramostim and synergy with immune checkpoint inhibitors to enhance efficacy and reduce treatment-related toxicity.


Lay abstract Immune checkpoint inhibitors are medications that help the immune system to fight cancer. Side effects with these medicines may occur because the immune system may attack healthy cells. Sargramostim is a medication that is similar to a protein in the body (GM-CSF). Studies have shown that sargramostim can fight cancer, including melanoma. When sargramostim is used with immune checkpoint inhibitors, the body's natural defense to fight cancer (the immune system) is boosted and some side effects are reduced. This article reviews how GM-CSF is thought to boost the immune system's response against cancer in the laboratory and in animal models. We also review the use of sargramostim alone and combined with ipilimumab in patients with advanced melanoma.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage , Immune Checkpoint Inhibitors/administration & dosage , Melanoma/drug therapy , Animals , Drug Synergism , Humans , Recombinant Proteins/administration & dosage
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