COMBINATION THERAPY INVOLVING ANTI-CD39 ANTIBODIES AND ADOPTIVE CELL THERAPY

1 . A therapeutic composition comprising an antibody which binds to CD39 and an adoptive cell therapy composition.

2 . The therapeutic composition according to claim 1 , wherein the adoptive cell therapy composition comprises NK cells, T cells, NKT cells, dendritic cells, macrophages, peripheral blood mononuclear cells (PBMCs), or a combination thereof.

3 . The therapeutic composition according to claim 1 , wherein the adoptive cell therapy composition comprises engineered cells expressing a heterologous T cell receptor (TCR) and/or a chimeric antigen receptor (CAR).

4 . The therapeutic composition according to claim 3 , wherein the engineered cells are T cells.

5 : The therapeutic composition according to claim 3 , wherein the engineered cells express a CAR comprising an extracellular binding moiety that specifically binds a tumor-associated antigen (TAA).

6 . The therapeutic composition of claim 5 , wherein the TAA is a B cell antigen.

7 . The therapeutic composition according to claim 6 , wherein the CAR comprises an anti-CD19 binding moiety.

8 . The therapeutic composition according to claim 5 , wherein the TAA is a melanoma antigen.

9 . The therapeutic composition according to claim 8 , wherein the melanoma antigen is gp100.

10 . The therapeutic composition according to claim 5 , wherein the CAR comprises an extracellular binding moiety, a transmembrane domain, and an intracellular domain that triggers the activation and/or proliferation of lymphocytes.

11 . The therapeutic composition according to claim 10 , wherein the intracellular domain comprises a CD3 signaling domain.

12 . The therapeutic composition according to claim 10 , wherein the CAR further comprises at least one costimulatory domain.

13 . The therapeutic composition according to claim 12 , wherein the CAR comprises a CD28 or 4-1BB costimulatory domain.

14 . The therapeutic composition according to claim 3 , wherein the engineered cells express the heterologous TCR.

15 . The therapeutic composition according to claim 14 , wherein the heterologous TCR specifically binds a TAA.

16 . The therapeutic composition according to claim 15 , wherein the TAA is a melanoma antigen.

17 . The therapeutic composition according to claim 16 , wherein TAA is gp100.

18 . The therapeutic composition of claim 17 , wherein the heterologous TCR is a pmel-1 TCR.

19 . The therapeutic composition according to any of the above claims, wherein the adoptive cell therapy composition comprises CD8+ T cells.

20 . The therapeutic composition according to claim 1 , wherein the antibody which binds to CD39 comprises a heavy chain variable region (VH) and a light chain variable region (VL), the VH and/or VL together comprising 1, 2, 3, 4, 5, or 6 of:

(a) a VHCDR1 having the sequence set forth in any one of SEQ ID NOs: 1-21 or SEQ ID NOs: 259-263,

(b) a VHCDR2 having the sequence set forth in any one of SEQ ID NOs: 24-42 or SEQ ID NOs: 265-269,

(c) a VHCDR3 having the sequence set forth in any one of SEQ ID NOs: 45-72 or SEQ ID NOs: 271-275,

(d) a VLCDR1 having the sequence set forth in any one of SEQ ID NOs: 75-89 or SEQ ID NOs: 277-281,

(e) a VLCDR2 having the sequence set forth in any one of SEQ ID NOs: 92-107 or SEQ ID NOs: 283-287, and

(f) a VLCDR3 having the sequence set forth in any one of SEQ ID NOs: 110-135 or SEQ ID NOs: 289-293.

21 - 49 . (canceled)