Novel Immune Checkpoint Inhibitors

A method of treating cancer in a human patient comprising

• a) providing a sample from the patient,
• b) measuring FGL1 expression level in said sample,
• c) comparing FGL1 expression to a control,
• d) identifying the patient as likely responsive to treatment with at least one antibody specifically inhibiting the interaction of FGL1 with LAG3 when FGL1 expression level has been measured as elevated compared to the control, and
• e) administering an effective amount of said antibody specifically inhibiting the interaction of FGL1 with LAG3 to the patient.

A method of predicting the responsiveness of a human cancer patient comprising

• (a) providing a sample from the patient,
• (b) determining FGL1 expression level in said sample,
• (c) comparing FGL1 expression to a control,
• (d) identifying the patient as likely responsive to treatment with an immune checkpoint inhibitory antibody, preferably an antibody that specifically inhibits the interaction of FGL1 with LAG3, when FGL1 expression level has been determined as elevated compared to the control, or identifying the patient as less likely responsive when FGL1 expression has been determined as not elevated compared to the control;
• and optionally
• (e) further comprising a step of administering to the cancer patient an immune checkpoint inhibitory antibody, preferably an antibody that specifically inhibits the interaction of FGL1 with LAG3.

A method for screening for an immune checkpoint inhibitory antibody comprising

• (a) providing a FGL1 protein, preferably comprising at least the fibrinogen domain of human FGL1;
• (b) providing a LAG3 protein, preferably comprising at least domains 1 and 2 of human LAG3;
• (c) contacting said FGL1 protein and said LAG3 protein in the presence of an antibody to be screened;
• (d) determining binding of said FGL1 protein to said LAG3 protein;
• and
• (e) identifying the antibody to be screened as an antibody that specifically inhibits interaction of said FGL1 protein with said LAG3 protein if the binding of said FGL1 protein and said LAG3 protein is reduced compared to the binding of said FGL1 protein and said LAG3 protein in the absence of said antibody to be screened.

A method for screening for a small molecule that inhibits the binding of FGL1 to LAG3, comprising

• a) providing a FGL1 protein, preferably comprising at least the fibrinogen domain of human FGL1;
• (b) providing a LAG3 protein, preferably comprising at least domains 1 and 2 of human LAG3;
• (c) contacting said FGL1 protein and said LAG3 protein in the presence of a small molecule, e.g. from a compound library, e.g. in the format of a high throughput screen,
• (d) determining binding of said FGL1 protein to said LAG3 protein in the presence and in the absence of said small molecule;
• and
• (e) identifying a small molecule that specifically inhibits binding of said FGL1 protein to said LAG3 protein as a FGL1-LAG3 checkpoint inhibitor molecule.

A method of treating cancer in a human patient comprising

• a) providing a sample from the patient,
• b) measuring FGL1 expression level in said sample,
• c) comparing FGL1 expression to a control,
• d) identifying the patient as likely responsive to treatment with an anti-FGL1 antibody when FGL1 expression level has been determined to be elevated, compared to the control, and
• e) administering an effective amount of an anti-FGL1 antibody to the patient.