Abstract: The present invention provides methods for treating a subject infected with 2019 coronavirus (SARS-CoV-2) comprising administering to the subject a therapeutically effective amount of a GM-CSF antagonist or a therapeutically effective amount of a GM-CSF antagonist and a second drug, including an anti-viral agent, an anti-SARS-CoV-2 vaccine, and serum containing human polyclonal antibodies to SARS-CoV-2.

Abstract: This document provides methods and materials involved in treating cancer. For example, chimeric antigen receptor T cells having reduced levels of GM-CSF are provided. Also provided as methods for making and using chimeric antigen receptor T cells having reduced levels of GM-CSF.

Abstract: Methods of inhibiting or reducing the incidence or the severity of immunotherapy-related toxicity in a subject, the method comprising a step of administering a recombinant hGMCSF antagonist to the subject, wherein said administering inhibits or reduces the incidence or the severity of immunotherapy-related toxicity in said subject, are provided. An hGMCSF antagonist for use in methods of inhibiting or reducing the incidence or the severity of immunotherapy-related toxicity in a subject also are provided.

Abstract: The present invention provides methods for treating a subject infected with 2019 coronavirus (SARS-CoV-2) comprising administering to the subject a therapeutically effective amount of a GM-CSF antagonist or a therapeutically effective amount of a GM-CSF antagonist and a second drug, including an anti-viral agent, an anti-SARS-CoV-2 vaccine, and serum containing human polyclonal antibodies to SARS-CoV-2.

Abstract: This invention provides chimeric antigen receptors (CARs) targeting human EphA3 and dual targeting CARs that bind to human EphA3 and to human mutant epidermal growth factor receptor variant III (EGFRvIII). This invention also relates to CAR-T cells comprising the provided CARs or the dual targeting CARs. Methods for treating a solid tumor cancer by administering the CARs are provided.

Abstract: The present invention provides methods for treating a subject infected with 2019 coronavirus (SARS-CoV-2) comprising administering to the subject a therapeutically effective amount of a GM-CSF antagonist or a therapeutically effective amount of a GM-CSF antagonist and a second drug, including an anti-viral agent, an anti-SARS-CoV-2 vaccine, and serum containing human polyclonal antibodies to SARS-CoV-2.

Abstract: This document provides methods and materials involved in treating cancer. For example, chimeric antigen receptor T cells having reduced levels of GM-CSF are provided.

Abstract: Methods for reducing blood-brain barrier disruption in a subject treated with immunotherapy, the method comprising administering a recombinant GM-CSF antagonist to the subject. Methods for preserving blood-brain barrier integrity in a subject treated with immunotherapy, the method comprising administering a recombinant hGM-CSF antagonist to the subject. Methods for decreasing or preventing CAR-T cell therapy-induced neuroinflammation in a subject in need thereof, the method comprising administering a recombinant GM-CSF antagonist to the subject. Methods for preventing or reducing blood-brain barrier in a subject treated with immunotherapy, the method comprising administering CAR-T cells having a GM-CSF gene knockout (GM-CSFk/o CAR-T cells) to the subject.

Abstract: Methods for neutralizing and/or removing human GM-CSF in a subject in need thereof, comprising administering to the subject CAR-T cells having a GM-CSF gene knockout (GM-CSFk/o CAR-T cells) are provided. Also provided are methods for GM-CSF gene inactivation or GM-CSF knockout (KO) in a cell comprising targeted genome editing or GM-CSF gene silencing. Methods for preventing/treating immunotherapy-related toxicity, comprising administering to the subject CAR-T cells having a GM-CSF gene inactivation or GM-CSF knockout (GM-CSFk/o CAR-T cells), wherein the GM-CSF gene is inactivated or knocked out and/or a recombinant GM-CSF antagonist are provided. Methods for reducing a level of a cytokine or chemokine other than GM-CSF in a subject having immunotherapy-related toxicity comprising administering to the subject a recombinant hGM-CSF antagonist are provided.

Abstract: The present invention provides methods for treating a subject infected with 2019 coronavirus (SARS-CoV-2) comprising administering to the subject a therapeutically effective amount of a GM-CSF antagonist or a therapeutically effective amount of a GM-CSF antagonist and a second drug, including an anti-viral agent, an anti-SARS-CoV-2 vaccine, and serum containing human polyclonal antibodies to SARS-CoV-2.

Abstract: Methods for reducing blood-brain barrier disruption in a subject treated with immunotherapy, the method comprising administering a recombinant GM-CSF antagonist to the subject. Methods for preserving blood-brain barrier integrity in a subject treated with immunotherapy, the method comprising administering a recombinant hGM-CSF antagonist to the subject. Methods for decreasing or preventing CAR-T cell therapy-induced neuroinflammation in a subject in need thereof, the method comprising administering a recombinant GM-CSF antagonist to the subject. Methods for preventing or reducing blood-brain barrier disruption in a subject treated with immunotherapy, the method comprising administering CAR-T cells having a GM-CSF gene knockout (GM-CSFk/o CAR-T cells) to the subject.

Abstract: Methods for neutralizing and/or removing human GM-CSF in a subject in need thereof, comprising administering to the subject CAR-T cells having a GM-CSF gene knockout (GM-CSFk/o CAR-T cells) are provided. Also provided are methods for GM-CSF gene inactivation or GM-CSF knockout (KO) in a cell comprising targeted genome editing or GM-CSF gene silencing. Methods for preventing/treating immunotherapy-related toxicity, comprising administering to the subject CAR-T cells having a GM-CSF gene inactivation or GM-CSF knockout (GM-CSFk/o CAR-T cells), wherein the GM-CSF gene is inactivated or knocked out and/or or a recombinant GM-CSF antagonist are provided. Methods for reducing a level of a cytokine or chemokine other than GM-CSF in a subject having immunotherapy-related toxicity comprising administering to the subject a recombinant hGM-CSF antagonist are provided.

Abstract: This document provides methods and materials involved in treating cancer. For example, chimeric antigen receptor T cells having reduced levels of GM-CSF are provided. Also provided as methods for making and using chimeric antigen receptor T cells having reduced levels of GM-CSF.

Abstract: Methods for reducing relapse rate or preventing occurrence of tumor relapse in a subject treated with immunotherapy, in an absence of an incidence of immunotherapy-related toxicity or in a presence of immunotherapy-related toxicity. Methods for reducing a level of a cytokine or chemokine other than GM-CSF in a subject having an incidence of immunotherapy-related toxicity, the methods comprising administering a recombinant GM-CSF antagonist to the subject. Methods for treating or preventing immunotherapy-related toxicity in a subject, the methods comprising administering to the subject chimeric antigen receptor-expressing T-cells (CAR-T cells), the CAR-T cells having a GM-CSF gene knockout (GM-CSFk/o CAR-T cells), and a recombinant hGM-CSF antagonist.

Abstract: This invention provides chimeric antigen receptors (CARs) targeting human EphA3 and dual targeting CARs that bind to human EphA3 and to human mutant epidermal growth factor receptor variant III (EGFRvIII). This invention also relates to CAR-T cells comprising the provided CARs or the dual targeting CARs. Methods for treating a solid tumor cancer by administering the CARs are provided.

Abstract: Methods for reducing relapse rate or preventing occurrence of tumor relapse in a subject treated with immunotherapy, in an absence of an incidence of immunotherapy-related toxicity or in a presence of immunotherapy-related toxicity. Methods for reducing a level of a cytokine or chemokine other than GM-CSF in a subject having an incidence of immunotherapy-related toxicity, the methods comprising administering a recombinant GM-CSF antagonist to the subject. Methods for treating or preventing immunotherapy-related toxicity in a subject, the methods comprising administering to the subject chimeric antigen receptor-expressing T-cells (CAR-T cells), the CAR-T cells having a GM-CSF gene knockout (GM-CSFk/o CAR-T cells), and a recombinant hGM-CSF antagonist.

Abstract: Methods of inhibiting or reducing the incidence or the severity of immunotherapy-related toxicity in a subject, the method comprising a step of administering a recombinant hGM-CSF antagonist to the subject, wherein said administering inhibits or reduces the incidence or the severity of immunotherapy-related toxicity in said subject, are provided. An hGM-CSF antagonist for use in methods of inhibiting or reducing the incidence or the severity of immunotherapy-related toxicity in a subject also are provided.

Abstract: The invention provides methods for generating human antibodies with the specificity of a reference antibody by replacement of portions of the VH and VL sequences of the reference antibody with sequences from human antibody repertoires. The invention also provides novel compositions comprising hybrid immunoglobulin variable domains containing a combination of frameworks (FRs) and CDRs from different antibody clones.

Abstract: Methods for reducing relapse rate or preventing occurrence of tumor relapse in a subject treated with immunotherapy, in an absence of an incidence of immunotherapy-related toxicity or in a presence of immunotherapy-related toxicity. Methods for reducing a level of a cytokine or chemokine other than GM-CSF in a subject having an incidence of immunotherapy-related toxicity, the methods comprising administering a recombinant GM-CSF antagonist to the subject. Methods for treating or preventing immunotherapy-related toxicity in a subject, the methods comprising administering to the subject chimeric antigen receptor-expressing T-cells (CAR-T cells), the CAR-T cells having a GM-CSF gene knockout (GM-CSFk/o CAR-T cells), and a recombinant hGM-CSF antagonist.

Abstract: Methods of inhibiting or reducing the incidence or the severity of immunotherapy-related toxicity in a subject, the method comprising a step of administering a recombinant hGM-CSF antagonist to the subject, wherein said administering inhibits or reduces the incidence or the severity of immunotherapy-related toxicity in said subject, are provided. An hGM-CSF antagonist for use in methods of inhibiting or reducing the incidence or the severity of immunotherapy-related toxicity in a subject also are provided.