Combination therapy with targeted 4-1BB (CD137) agonists/anti-FAP binding domain and anti-CEA/anti-CD3 bispecific antibody

A method for treating cancer in a subject, wherein the method comprises administering to the subject an effective amount of a T-cell activating anti-carcinoembryonic antigen (CEA)/anti-CD3 bispecific antibody and an effective amount of a 4-1BB agonist that binds to 4-1BB comprising at least one antigen binding domain capable of specific binding to fibroblast activation protein (FAP),

• wherein said treating comprises alleviating symptoms of the cancer, diminishing pathological consequences of the cancer, delaying progression of the cancer, decreasing the rate of disease progression of the cancer, amelioration or palliation of the disease state of the cancer, remission of the cancer, or improving prognosis of the cancer;
• and
• wherein the at least one antigen binding domain capable of specific binding to FAP comprises:
• a heavy chain variable region (VHFAP) comprising (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:15, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO:16, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO:17, and
• a light chain variable region (VLFAP) comprising (iv) CDR-L1 comprising the amino acid sequence of SEQ ID NO:18, (v) CDR-L2 comprising the amino acid sequence of SEQ ID NO:19, and (vi) CDR-L3 comprising the amino acid sequence of SEQ ID NO:20;
• and
• wherein the 4-1BB agonist that binds to 4-1BB comprises a first polypeptide and a second polypeptide that are linked to each other by a disulfide bond,
• wherein the first polypeptide comprises the amino acid sequence of SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, or SEQ ID NO:32 and the second polypeptide comprises the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, or SEQ ID NO:8.