Combination Of T-Cell Redirecting Multifunctional Antibodies With Immune Checkpoint Modulators And Uses Thereof

A kit comprising

• (i) an immune checkpoint modulator and
• (ii) a T-cell redirecting multifunctional antibody, or an antigen binding fragment thereof, comprising:
• (a) a specificity against a T cell surface antigen;
• (b) a specificity against a cancer- and/or tumor-associated antigen;
• and
• (c) a binding site for human FcγRI, FcγRIIa and/or FcγRIII, wherein the antibody, or the antigen binding fragment thereof, binds with a higher affinity to human FcγRI, FcγRIIa and/or FcγRIII than to human FcγRIIb;
• for use in therapeutic treatment of a cancer disease, in particular in a human subject.

A composition comprising

• (i) an immune checkpoint modulator and
• (ii) a T-cell redirecting multifunctional antibody, or an antigen binding fragment thereof, comprising:
• (a) a specificity against a T cell surface antigen;
• (b) a specificity against a cancer- and/or tumor-associated antigen;
• and
• (c) a binding site for human FcγRI, FcγRIIa and/or FcγRIII, wherein the antibody, or the antigen binding fragment thereof, binds with a higher affinity to human FcγRI, FcγRIIa and/or FcγRIII than to human FcγRIIb.

A method for therapeutically treating cancer or initiating, enhancing or prolonging an anti-tumor-response in a subject in need thereof comprising administering to the subject

• (i) an immune checkpoint modulator and
• (ii) a T-cell redirecting multifunctional antibody, or an antigen binding fragment thereof, comprising:
• (a) a specificity against a T cell surface antigen;
• (b) a specificity against a cancer- and/or tumor-associated antigen;
• and
• (c) a binding site for human FcγRI, FcγRIIa and/or FcγRIII, wherein the antibody, or the antigen binding fragment thereof, binds with a higher affinity to human FcγRI, FcγRIIa and/or FcγRIII than to human FcγRIIb.

A method of prolonging T-cell activation in a subject comprising administering to a subject a combination of:

• (i) an immune checkpoint modulator and
• (ii) a T-cell redirecting multifunctional antibody, or an antigen binding fragment thereof, comprising:
• (a) a specificity against a T cell surface antigen;
• (b) a specificity against a cancer- and/or tumor-associated antigen;
• and
• (c) a binding site for human FcγRI, FcγRIIa and/or FcγRIII, wherein the antibody, or the antigen binding fragment thereof, binds with a higher affinity to human FcγRI, FcγRIIa and/or FcγRIII than to human FcγRIIb.

A combination therapy for therapeutically treating cancer, wherein the combination therapy comprises administration of

• (i) an immune checkpoint modulator and
• (ii) a T-cell redirecting multifunctional antibody, or an antigen binding fragment thereof, comprising:
• (a) a specificity against a T cell surface antigen;
• (b) a specificity against a cancer- and/or tumor-associated antigen;
• and
• (c) a binding site for human FcγRI, FcγRIIa and/or FcγRIII, wherein the antibody, or the antigen binding fragment thereof, binds with a higher affinity to human FcγRI, FcγRIIa and/or FcγRIII than to human FcγRIIb.