Anti-cd28 x anti-trop2 antibodies

A heterodimeric antibody comprising:

• a) a first monomer comprising:
• i) a single chain variable fragment (scFv);
• and
• ii) a first Fc domain, wherein the scFv is covalently attached to the N-terminus of the first Fc domain using a domain linker;
• b) a second monomer comprising, from N-terminal to C-terminal, a VH1-CH1-hinge-CH2-CH3, wherein VH1 is a first variable heavy domain and CH2-CH3 is a second Fc domain;
• and
• c) a light chain comprising, from N-terminal to C-terminal, VL1-CL, wherein VL1 is a first variable light domain and CL is a constant light domain,
• wherein the scFv comprises a second VH domain (VH2), a scFv linker, and a second variable light domain (VL2),
• wherein the VH1 and the VL1 together form a first antigen binding domain (ABD) and the VH2 and the VL2 together form a second ABD, and
• wherein one of the first ABD and second ABD is a CD28 binding domain and the other of the first ABD and second ABD is a tumor-associated calcium signal transducer 2 (TROP2) binding domain.

The heterodimeric antibody according to 104, wherein VH2 and VL2 are selected from one of the following:

• (1) a VH and VL of any of the CD28 binding domains from FIGS. 16, 19, and 22;
• or
• (2) (i) a VH from FIG. 16, 17, or 34;
• and (ii) a VL from FIG. 16, 18, or 36.

A heterodimeric antibody comprising:

• a) a first monomer comprising, from N-terminal to C-terminal, VH1-CH1-hinge-CH2-CH3-domain linker-scFv,
• wherein VH1 is a first variable heavy domain, and CH2-CH3 is a first Fc domain;
• b) a second monomer comprising, from N-terminal to C-terminal, a VH1-CH1-hinge-CH2-CH3, wherein VH1 is a first variable heavy domain and CH2-CH3 is a second Fc domain;
• and
• c) a first light chain comprising, from N-terminal to C-terminal, VL1-CL, wherein VL1 is a first variable light domain and CL is a constant light domain;
• and
• d) a second light chain comprising, from N-terminal to C-terminal, VL1-CL, wherein VL1 is a first variable light domain and CL is a constant light domain,
• wherein the scFv comprises a second VH domain (VH2), a scFv linker, and a second variable light domain (VL2),
• wherein the VH1 of the first monomer and the VL1 of the first light chain and the VH1 of the second monomer and the VL1 of the second light chain each form a first antigen binding domain (ABD), and the VH2 and the VL2 form a second ABD, and
• wherein one of the first and second ABDs bind human CD28 and the other of the first and second ABDs binds TROP2.

A multivalent antibody comprising:

• a) a first monomer comprising, from N-terminal to C-terminal, a VH1-CH1-hinge-CH2-CH3, wherein VH1 is a first variable heavy domain and CH2-CH3 is a first Fc domain;
• b) a second monomer comprising, from N-terminal to C-terminal, a VH2-CH1-hinge-CH2-CH3, wherein VH2 is a second variable heavy domain and CH2-CH3 is a second Fc domain;
• c) a first common light chain and second common light chain that each comprise a VL-CL, wherein VL is a variable domain and CL is a constant light domain;
• wherein the VH1 and the VL of the first common light chain form a first antigen binding domain (ABD) and the VH2 and the VL of the second common light chain together form a second ABD,
• wherein the first common light chain and second common light chain have the same amino acid sequence, and
• wherein one of the first ABD and second ABD is a CD28 binding domain and the other of the first ABD and second ABD is a tumor-associated calcium signal transducer 2 (TROP2) binding domain.

A multivalent antibody comprising:

• a) a first monomer comprising, from N-terminal to C-terminal, a VH1-CH1-linker-VH1-CH1-hinge-CH2-CH3, wherein the VH1s are each a first variable heavy domain and CH2-CH3 is a first Fc domain;
• b) a second monomer comprising, from N-terminal to C-terminal, a VH2-CH1-hinge-CH2-CH3, wherein VH2 is a second variable heavy domain and CH2-CH3 is a second Fc domain;
• c) a first common light chain, a second common light chain, and third common light chain that each comprise a VL-CL, wherein VL is a variable domain and CL is a constant light domain;
• wherein the VH1s of the first monomer each pair with a VL of the first common light chain or second common light to form two first antigen binding domains (ABDs) and the VH2 and the VL of the third common light chain together form a second ABD,
• wherein the first common light chain, second common light chain, and third common light chain each have the same amino acid sequence, and
• wherein the first ABDs are each a CD28 binding domain and the second ABD is a tumor-associated calcium signal transducer 2 (TROP2) binding domain, or the first ABDs are each a TROP2 binding domain and the second ABD is a CD28 binding domain.