FUSION CONSTRUCTS AND METHODS OF USING THEREOF

1 . A method of treating cancer, the method comprising administering to a patient in need thereof either:

(a) a fusion protein comprising:

a first component that is an antibody, or a functional fragment or variant thereof; and

a second component that is either: a cytokine trap, or a functional fragment or variant thereof; or an adenosine deaminase (ADA), or a functional fragment or variant thereof;

or

(b) a polynucleotide encoding the same.

2 - 13 . (canceled)

14 . The method of claim 1 , wherein the first component of the fusion protein binds to a tumor antigen expressed on the surface of a tumor cell, wherein the tumor antigen is selected from CD19, BCMA, CD23, BAFF-R, GPRC5D, CD44, CAIX, CD5, CD30, CD70, CD44v6, CD44v7, CD44v8, CD174, CD28, CD128, CD138, CS1, CLL-1, L1-CAM, FAP, ROR1, CEA, EGP-2, EGP-40, HER2, HER3, Folate-binding Protein, GD2, GD3, IL-13R-a2, IL-11Ra, EphA2, CSPG4, KDR, EDB-F, mesothelin, CD22, EGFR, Folate receptor «, MUC-1, MUC-4, MUC-16, MAGE-A1, h5T4, PSMA, PSCA, GPC3, c-met, TAG-72, EGFR, CD20, EGFRVIII, CD123, and VEGF-R2.

15 - 20 . (canceled)

21 . The method of claim 1 , wherein the first component of the fusion protein comprises:

(a) a VL-region comprising a polypeptide that is at least 80% identical to any one of SEQ ID NOs: 417-428; and

(b) a VH-region comprising a polypeptide that is at least 80% identical to any one of SEQ ID NOs: 390-403.

22 . (canceled)

23 . The method of claim 1 , wherein:

(a) the first component of the fusion protein comprises: a VL-region comprising a polypeptide that is at least 80% identical to SEQ ID NO: 426; and a VH region comprising a polypeptide that is at least 80% identical to SEQ ID NO: 399; and

(b) the second component of the fusion protein is a cytokine trap comprising a sequence that is at least 80% identical to SEQ ID NO: 14.

24 - 29 . (canceled)

30 . The method of claim 1 , wherein the first component of the fusion protein comprises:

(a) a VL-region comprising a polypeptide that is at least 80% identical to any one of SEQ ID NOs: 449-453; and

(b) a VH-region comprising a polypeptide that is at least 80% identical to any one of SEQ ID NOs: 444-448.

31 - 62 . (canceled)

63 . The method of claim 1 , wherein the cytokine trap is a TGF-β cytokine trap comprising either:

(a) a transforming growth factor beta receptor II (TGFβRII);

(b) a TGFβR extracellular domain;

(c) a TGFβRII extracellular domain;

(d) an anti-TGF-β antibody;

(e) a TGF-β inhibitory peptide;

(f) a TGF-β antagonistic peptide: or

(g) a functional fragment or variant of any of (a) thru (f).

64 - 68 . (canceled)

69 . The method of claim 1 , wherein the cytokine trap comprises a polypeptide that is at least 80% identical to any one of SEQ ID NOs: 14, 141, 142.

70 . The method of claim 1 , wherein the cytokine trap is a TGF-β cytokine trap comprising a polypeptide that is at least 80% identical to SEQ ID NO: 14.

71 - 74 . (canceled)

75 . The method of claim 1 , wherein the cytokine trap is a TGF-β cytokine trap comprising an anti-TGF-β antibody, or an antigen-binding fragment or variant thereof, wherein the anti-TGF-β antibody comprises:

(a) a VH region comprising a polypeptide that is at least 80% identical to any one of SEQ ID NOs: 166, 168, 169, 171, 173, and 175; and/or

(b) a VL region comprising a polypeptide that is at least 80% identical to any one of SEQ ID NOs: 165, 167, 170, 172, 174, 176, and 178.

76 - 83 . (canceled)

84 . The method of claim 1 , wherein the second component of the fusion protein is an ADA, or a functional fragment or variant thereof.

85 - 86 . (canceled)

87 . The method of claim 84 , wherein the ADA comprises a polypeptide that is at least 80% identical to any one of SEQ ID NOs: 273-279 and 284.

88 . The method of claim 1 , wherein the first and second components of the fusion protein are connected by a linker comprising:

(a) (G4S) n , wherein n is 2, 3, 4, 5, or 6 (SEQ ID NO: 555);

(b) (Gly) n wherein n is 6, 7, or 8 (SEO ID NO: 33);

(c) (EAAAK) n , wherein n is 1, 2, 3, 4, 5, or 6 (SEQ ID NO: 34);

(d) A (EAAAK) 4 ALEA (EAAAK) 4 A (SEO ID NO: 31); and/or

(e) a sequence of any one of SEO ID NOs: 17-34.

89 - 111 . (canceled)

112 . The method of claim 1 , further comprising administering to the patient a fusion protein comprising IL-15 and IL-15Rα.

113 - 118 . (canceled)

119 . The method of claim 1 , further comprising administering to the patient an effective amount of T cells engineered to express an exogenous receptor.

120 - 124 . (canceled)

125 . The method of claim 1 , wherein the effective amount of engineered T-cells is at least 10 2 cells/kg.

126 - 130 . (canceled)

131 . The method of claim 1 , wherein the first component of the fusion protein comprises:

(a) a VL region comprising the sequence of any one of SEQ ID NOs: 423, 425, and 426; and

(b) a VH region comprising the sequence of SEQ ID NO: 399.

132 . The method of claim 131 , wherein the first component of the fusion protein comprises a VL region comprising the sequence of any one of SEQ ID NO: 423.

133 . The method of claim 131 , wherein the first component of the fusion protein comprises a VL region comprising the sequence of any one of SEQ ID NO: 425.

134 . The method of claim 131 , wherein the first component of the fusion protein comprises a VL region comprising the sequence of any one of SEQ ID NO: 426.

135 . The method of claim 131 , wherein:

(a) the first component of the fusion protein comprises:

(i) a VL region comprising the sequence of SEQ ID NO: 426; and

(ii) a VH region comprising the sequence of SEQ ID NO: 399; and

(b) the second component of the fusion protein is a cytokine trap comprising the sequence of SEQ ID NO: 14.