Abstract: Conditions necessary for antibodies to human PD-1 to have agonist activity are searched and an optimized agonist antibody is provided based on the conditions and used as a therapeutic for human inflammatory diseases. An agonist antibody to human PD-1 or a functional fragment thereof, wherein the antibody or a functional fragment thereof binds to domain #7 of human PD-1 as shown in SEQ ID NO: 9 is provided.

Abstract: The present invention provides a novel combination therapy with PD-1 blockade therapy. A pharmaceutical composition which comprises a substance capable of enhancing T cell receptor (TCR) signaling and is administered before, after or simultaneously with the administration of a PD-1 signaling inhibitor. A drug which enhances PD-1 signaling inhibitory activity, comprising a CD45 inhibitor and/or a cell. A TCR signaling enhancer comprising a CD45 inhibitor and/or a cell.

Abstract: A novel therapeutic strategy for the anti-PD-1 antibody therapy is provided. A pharmaceutical composition which comprises at least one substance selected from the group consisting of the following (i) to (iii) and is administered before, after or simultaneously with the administration of a PD-1 signal inhibitor: (i) ROS generators and substances that regulate downstream signaling pathways thereof, (ii) substances exhibiting an uncoupling effect and substances that regulate downstream signaling pathways thereof, and (iii) amino acids.

Abstract: A novel therapeutic strategy for the anti-PD-1 antibody therapy is provided. A pharmaceutical composition which comprises at least one substance selected from the group consisting of the following (i) to (iii) and is administered before, after or simultaneously with the administration of a PD-1 signal inhibitor: (i) ROS generators and substances that regulate downstream signaling pathways thereof, (ii) substances exhibiting an uncoupling effect and substances that regulate downstream signaling pathways thereof, and (iii) amino acids.

Abstract: A novel use of agonist to PD-1 is developed. Provided is a pharmaceutical composition for treating or preventing Th2-mediated diseases, the composition comprising an effective amount of a PD-1 agonist.

Abstract: The present invention provides markers for judging the efficacy of therapy with a PD-1 signal inhibitor before or at an early stage of the therapy. As biomarkers for predicting or judging the efficacy of therapy with a PD-1 signal inhibitor, surrogate indicators of metabolic changes relating to mitochondrial activity in T cells and/or T cell activation in a subject are used. As such indicators, intestinal flora-related metabolites in the serum or plasma, energy metabolism-related metabolites in the serum or plasma, amino acid metabolism-related metabolites and/or derivatives thereof in the serum of plasma, oxygen consumption rate and/or ATP turnover in peripheral blood CD8+ cells, amino acids in T cells, and T-bet in peripheral blood CD8+ cells may be used.

Abstract: The present invention provides a novel therapeutic strategy for anti-PD-1 antibody therapy. The present invention relates to a pharmaceutical composition which increases the function of oxidative phosphorylation in T cells; and a pharmaceutical composition which has an action for increasing the function of oxidative phosphorylation in T cells and is administered before, after or simultaneously with the administration of a PD-1 signaling inhibitor.

Abstract: A marker for judging the efficacy of therapy with a PD-1 signal inhibitor-containing drug before or at an early stage of the therapy is provided.

Abstract: Disclosed is a method for assisting a determination of an efficacy of an immune checkpoint inhibitor, the method comprising: measuring a free protein marker in a liquid sample collected from a subject; and determining the efficacy of the immune checkpoint inhibitor in the subject based on a result of the measurement, wherein the free protein marker is at least one selected from free Cytotoxic T lymphocyte antigen-4 (CTLA-4), free Programmed cell death-1 (PD-1) and free Programmed cell death-ligand 1 (PD-L1).

Abstract: Compositions for cancer or infection treatment via immunopotentiation caused by inhibition of immunosuppressive signal induced by PD-1, PD-L1, or PD-L2 and therapies using them, immunopotentiative substrates included as the active ingredient, screening methods of the substrates for cancer or infection treatment, cell lines used for the screening methods, evaluation methods that selects the substrates for cancer treatment, and carcinoma cell transplanted mammals used for the evaluation methods. The compositions of the present invention that inhibits the function of PD-1, PD-L1, or PD-L2 are useful for cancer or infection treatment.

Abstract: A novel therapeutic strategy for the anti-PD-1 antibody therapy is provided. A pharmaceutical composition which comprises at least one substance selected from the group consisting of the following (i) to (iii) and is administered before, after or simultaneously with the administration of a PD-1 signal inhibitor: (i) ROS generators and substances that regulate downstream signaling pathways thereof, (ii) substances exhibiting an uncoupling effect and substances that regulate downstream signaling pathways thereof, and (iii) amino acids.

Abstract: The present invention relates to a method for determining cancer, the method comprising the steps of: measuring free PD-L1 (Programmed cell death-ligand 1) and free PD-1 (Programmed cell death-1) as free protein markers in a liquid sample collected from a subject, and determining whether or not the liquid sample is a sample collected from a subject suffering from cancer, based on measurement results.

Abstract: The present invention relates to a substance specific to human PD-1 comprising a part that recognizes human PD-1, a part that recognizes a membrane protein in cell membrane of human PD-1-expressing cells, and linkers. Since the substance specific to human PD-1 selectively can recognize human PD-1 and a membrane protein on cell membrane of human PD-1-expressing cells and can transmit inhibitory signal of human PD-1, it is useful for therapy and/or prevention of diseases caused by immunopathy.

Abstract: Compositions for cancer or infection treatment via immunopotentiation caused by inhibition of immunosuppressive signal induced by PD-1, PD-L1, or PD-L2 and therapies using them, immunopotentiative substrates included as the active ingredient, screening methods of the substrates for cancer or infection treatment, cell lines used for the screening methods, evaluation methods that selects the substrates for cancer treatment, and carcinoma cell transplanted mammals used for the evaluation methods. The compositions of the present invention that inhibits the function of PD-1, PD-L1, or PD-L2 are useful for cancer or infection treatment.

Abstract: Compositions for cancer or infection treatment via immunopotentiation caused by inhibition of immunosuppressive signal induced by PD-1, PD-L1, or PD-L2 and therapies using them, immunopotentiative substrates included as the active ingredient, screening methods of the substrates for cancer or infection treatment, cell lines used for the screening methods, evaluation methods that selects the substrates for cancer treatment, and carcinoma cell transplanted mammals used for the evaluation methods. The compositions of the present invention that inhibits the function of PD-1, PD-L1, PD-L2 are useful for cancer or infection treatment.

Abstract: Compositions for cancer or infection treatment via immunopotentiation caused by inhibition of immunosuppressive signal induced by PD-1, PD-L1, or PD-L2 and therapies using them, immunopotentiative substrates included as the active ingredient, screening methods of the substrates for cancer or infection treatment, cell lines used for the screening methods, evaluation methods that select the substrates for cancer treatment, and carcinoma cell transplanted mammals used for the evaluation methods. The compositions of the present invention that inhibits the function of PD-1, PD-L1, or PD-L2 are useful for treatment of cancer or infection.

Abstract: Compositions for cancer or infection treatment via immunopotentiation caused by inhibition of immunosuppressive signal induced by PD-1, PD-L1, or PD-L2 and therapies using them, immunopotentiative substrates included as the active ingredient, screening methods of the substrates for cancer or infection treatment, cell lines used for the screening methods, evaluation methods that selects the substrates for cancer treatment, and carcinoma cell transplanted mammals used for the evaluation methods. The compositions of the present invention that inhibits the function of PD-1, PD-L1 PD-L2 are useful for cancer or infection treatment.

Abstract: Compositions for cancer or infection treatment via immunopotentiation caused by inhibition of immunosuppressive signal induced by PD-1, PD-L1, or PD-L2 and therapies using them, immunopotentiative substrates included as the active ingredient, screening methods of the substrates for cancer or infection treatment, cell lines used for the screening methods, evaluation methods that selects the substrates for cancer treatment, and carcinoma cell transplanted mammals used for the evaluation methods. The compositions of the present invention that inhibits the function of PD-1, PD-L1, PD-L2 are useful for cancer or infection treatment.

Abstract: Compositions for cancer or infection treatment via immunopotentiation caused by inhibition of immunosuppressive signal induced by PD-1, PD-L1, or PD-L2 and therapies using them, immunopotentiative substrates included as the active ingredient, screening methods of the substrates for cancer or infection treatment, cell lines used for the screening methods, evaluation methods that selects the substrates for cancer treatment, and carcinoma cell transplanted mammals used for the evaluation methods. The compositions of the present invention that inhibits the function of PD-1, PD-L1, or PD-L2 are useful for cancer or infection treatment.

Abstract: Compositions for cancer or infection treatment via immunopotentiation caused by inhibition of immunosuppressive signal induced by PD-1, PD-L1, or PD-L2 and therapies using them, immunopotentiative substrates included as the active ingredient, screening methods of the substrates for cancer or infection treatment, cell lines used for the screening methods, evaluation methods that selects the substrates for cancer treatment, and carcinoma cell transplanted mammals used for the evaluation methods. The compositions of the present invention that inhibits the function of PD-1, PD-L1, or PD-L2 are useful for cancer or infection treatment.