Anti-CD28 × Anti-PSMA Antibodies

Abstract

Provided herein are novel anti-CD28×anti-PSMA antibodies and methods of using such antibodies for the treatment of PSMA-associated cancers. The subject anti-CD28×anti-PSMA antibodies are capable of agonistically binding to CD28 costimulatory molecules on T cells and PSMA on tumor cells. Thus, such antibodies selectively enhance anti-tumor activity at tumor sites while minimizing peripheral toxicity. The subject antibodies provided herein are particularly useful in combination with other anti-cancer therapies (e.g., anti-CD3×anti-PSMA antibodies) for the treatment of prostate cancer.

Description

[Technical Field]

[0001] Priority claim This application claims priority to and benefit of U.S. Provisional Application No. 63 / 313,233, filed February 23, 2022, the contents of which are hereby incorporated by reference in their entirety.

[0002] Sequence Listing This application contains a Sequence Listing that has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. Said XML copy, created on February 22, 2023, is named 067461-5297-WO_SL.xml and is 1,295,846 bytes in size. [Background technology]

[0003] Prostate cancer (PC) is one of the most common cancers in men, and end-stage (castration-resistant) prostate cancer has no curative treatment options. Prostate-specific membrane antigen (PSMA), a type II transmembrane protein with a large extracellular domain, has long attracted interest as a therapeutic target. PSMA is highly overexpressed in PC compared with normal tissue, and its expression has been shown to correlate with malignancy. Previous attempts to target PSMA include antibody-based radiation therapy and antibody-drug conjugates, which have shown some success but can be hampered by the inherent toxicity of these modalities.

[0004] Antibody-based therapeutics have been used successfully to treat a variety of diseases, including cancer. An increasingly widespread avenue being explored is the engineering of a single immunoglobulin molecule that co-engages two different antigens. Such alternative antibody formats that engage two different antigens are often referred to as bispecific antibodies. One particular approach for bispecific antibodies is to engineer a single immunoglobulin molecule that co-engages two different antigens. +The goal is to engineer a first binding domain that engages CD3 and a second binding domain that engages an antigen associated with or upregulated on cancer cells (e.g., PSMA) to redirect T cells to destroy cancer cells.

[0005] However, TILs lose their cytotoxicity over time due to the upregulation of inhibitory immune checkpoints. Although checkpoint blockade has demonstrated increased clinical response rates compared to other treatment options, many patients still fail to achieve a response to checkpoint blockade. Engagement of costimulatory receptors on TILs can provide positive signals that can overcome the negative signals of immune checkpoints. Preclinical and clinical studies of agonistic costimulatory receptor antibodies have indeed demonstrated that agonism of costimulatory receptors can result in excellent antitumor responses, activating T cells to attack tumor cells.

[0006] It is also important for cancer therapy to specifically destroy tumor cells while minimizing peripheral toxicity, thereby improving antitumor activity. In this context, it is important that costimulatory signals are provided only to T cells in the presence of target tumor cells. However, agonism of costimulatory receptors with monospecific full-length antibodies is unlikely to be discriminatory with respect to TILs, peripheral T cells, and autoantigen-reactive T cells that contribute to autoimmune toxicity. Therefore, there remains a need for novel immune response enhancing compositions for the treatment of cancer, including PSMA-associated cancers. Summary of the Invention

[0007] Provided herein are novel anti-CD28×anti-PSMA antibodies and methods of using such antibodies for the treatment of PSMA-associated cancers. The subject anti-CD28×anti-PSMA antibodies are capable of agonistically binding to the CD28 costimulatory molecule on T cells and PSMA on tumor cells. Thus, such antibodies selectively enhance anti-tumor activity at the tumor site while minimizing peripheral toxicity. The subject antibodies provided herein are particularly useful in combination with other anti-cancer therapies (e.g., anti-CD3×anti-PSMA antibodies) for the treatment of prostate cancer.

[0008] In a first aspect, provided herein are heterodimeric anti-CD28 x anti-PSMA antibodies in a 1+1 Fab-scFv-Fc format. These antibodies comprise a) a first monomer; b) a second monomer; and c) a light chain. The first monomer comprises i) a single-chain variable fragment (scFv); and ii) a first Fc domain, where the scFv is covalently linked to the N-terminus of the first Fc domain using a domain linker. The second monomer comprises, from N- to C-terminus, VH1-CH1-hinge-CH2-CH3, where VH1 is the first variable heavy domain and CH2-CH3 are the second Fc domain. The light chain comprises, from N- to C-terminus, VL1-CL, where VL1 is the first variable light domain and CL is the constant light domain. The scFv comprises a second VH domain (VH2), an scFv linker, and a second variable light domain (VL2). VH1 and VL1 together form a first antigen-binding domain (ABD), and VH2 and VL2 together form a second ABD. Furthermore, one of the first and second ABDs binds CD28, and the other of the first and second ABDs binds prostate-specific membrane antigen (PSMA).

[0009] In some embodiments, the first ABD binds human CD28 and the second ABD binds PSMA. In certain embodiments, the first ABD binds PSMA and the second ABD binds human CD28.

[0010] In some embodiments, the scFv comprises, from N- to C-terminus, VH2-scFv linker-VL2. In certain embodiments, the scFv comprises, from N- to C-terminus, VL2-scFv linker-VH2.

[0011] In some embodiments, the first ABD binds human PSMA and VH1 and VL1 are selected from:

[0012] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 206; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 210; or

[0013] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 214; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 218; or

[0014] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 222; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 226; or

[0015] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 230; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 234; or

[0016] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 238; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 242; or

[0017] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 246; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 250; or

[0018] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 254; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 258; or

[0019] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 262; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 266; or

[0020] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 270; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 274; or

[0021] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 278; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 282; or

[0022] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 286; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 290; or

[0023] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 294; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 298; or

[0024] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 302; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 306; or

[0025] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 310; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 314; or

[0026] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 318; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 322; or

[0027] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 326; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 330; or

[0028] (i) VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of VH vhCDR1, vhCDR2, and vhCDR3, respectively, having the amino acid sequences of SEQ ID NO: 334; and (ii) VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of VL vlCDR1, vlCDR2, and vlCDR3, respectively, having the amino acid sequences of SEQ ID NO: 338.

[0029] In some embodiments, VH1 and VL1 are selected from:

[0030] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 207; a vhCDR2 having the amino acid sequence of SEQ ID NO: 208; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 209; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 211; a vlCDR2 having the amino acid sequence of SEQ ID NO: 212; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 213; or

[0031] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 215; a vhCDR2 having the amino acid sequence of SEQ ID NO: 216; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 217; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 219; a vlCDR2 having the amino acid sequence of SEQ ID NO: 220; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 221;

[0032] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 223; a vhCDR2 having the amino acid sequence of SEQ ID NO: 224; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 225; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 227; a vlCDR2 having the amino acid sequence of SEQ ID NO: 228; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 229; or

[0033] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 231; a vhCDR2 having the amino acid sequence of SEQ ID NO: 232; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 233; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 235; a vlCDR2 having the amino acid sequence of SEQ ID NO: 236; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 237; or

[0034] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 239; a vhCDR2 having the amino acid sequence of SEQ ID NO: 240; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 241; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 243; a vlCDR2 having the amino acid sequence of SEQ ID NO: 244; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 245; or

[0035] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 247; a vhCDR2 having the amino acid sequence of SEQ ID NO: 248; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 249; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 251; a vlCDR2 having the amino acid sequence of SEQ ID NO: 252; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 253; or

[0036] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 255; a vhCDR2 having the amino acid sequence of SEQ ID NO: 256; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 257; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 259; a vlCDR2 having the amino acid sequence of SEQ ID NO: 260; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 261; or

[0037] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 263; a vhCDR2 having the amino acid sequence of SEQ ID NO: 264; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 265; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 267; a vlCDR2 having the amino acid sequence of SEQ ID NO: 268; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 269; or

[0038] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 271; a vhCDR2 having the amino acid sequence of SEQ ID NO: 212; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 273; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 275; a vlCDR2 having the amino acid sequence of SEQ ID NO: 276; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 277; or

[0039] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 279; a vhCDR2 having the amino acid sequence of SEQ ID NO: 280; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 281; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 283; a vlCDR2 having the amino acid sequence of SEQ ID NO: 284; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 285; or

[0040] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 287; a vhCDR2 having the amino acid sequence of SEQ ID NO: 288; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 289; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 291; a vlCDR2 having the amino acid sequence of SEQ ID NO: 292; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 293; or

[0041] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 295; a vhCDR2 having the amino acid sequence of SEQ ID NO: 296; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 297; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 299; a vlCDR2 having the amino acid sequence of SEQ ID NO: 300; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 301; or

[0042] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 303; a vhCDR2 having the amino acid sequence of SEQ ID NO: 304; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 305; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 307; a vlCDR2 having the amino acid sequence of SEQ ID NO: 308; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 309; or

[0043] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 311; a vhCDR2 having the amino acid sequence of SEQ ID NO: 312; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 313; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 315; a vlCDR2 having the amino acid sequence of SEQ ID NO: 316; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 317; or

[0044] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 319; a vhCDR2 having the amino acid sequence of SEQ ID NO: 320; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 321; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 323; a vlCDR2 having the amino acid sequence of SEQ ID NO: 324; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 325; or

[0045] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 327; a vhCDR2 having the amino acid sequence of SEQ ID NO: 328; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 329; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 331; a vlCDR2 having the amino acid sequence of SEQ ID NO: 332; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 333; or

[0046] (i) VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 335; a vhCDR2 having the amino acid sequence of SEQ ID NO: 336; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 337; and (ii) VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 339; a vlCDR2 having the amino acid sequence of SEQ ID NO: 340; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 341.

[0047] In an exemplary embodiment, VH1 and VL1 are selected from the following:

[0048] (i) a VH1 having the amino acid sequence of SEQ ID NO: 206; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 210; or

[0049] (i) a VH1 having the amino acid sequence of SEQ ID NO: 214; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 218; or

[0050] (i) a VH1 having the amino acid sequence of SEQ ID NO: 222; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 226; or

[0051] (i) a VH1 having the amino acid sequence of SEQ ID NO: 230; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 234; or

[0052] (i) a VH1 having the amino acid sequence of SEQ ID NO: 238; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 242; or

[0053] (i) a VH1 having the amino acid sequence of SEQ ID NO: 246; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 250; or

[0054] (i) a VH1 having the amino acid sequence of SEQ ID NO: 254; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 258; or

[0055] (i) a VH1 having the amino acid sequence of SEQ ID NO: 262; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 266; or

[0056] (i) a VH1 having the amino acid sequence of SEQ ID NO: 270; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 274; or

[0057] (i) a VH1 having the amino acid sequence of SEQ ID NO: 278; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 282; or

[0058] (i) a VH1 having the amino acid sequence of SEQ ID NO: 286; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 290; or

[0059] (i) a VH1 having the amino acid sequence of SEQ ID NO: 294; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 298; or

[0060] (i) a VH1 having the amino acid sequence of SEQ ID NO: 302; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 306; or

[0061] (i) a VH1 having the amino acid sequence of SEQ ID NO: 310; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 314; or

[0062] (i) a VH1 having the amino acid sequence of SEQ ID NO: 318; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 322; or

[0063] (i) a VH1 having the amino acid sequence of SEQ ID NO: 326; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 330; or

[0064] (i) VH1 having the amino acid sequence of SEQ ID NO: 334; and (ii) VL1 having the amino acid sequence of SEQ ID NO: 338.

[0065] In some embodiments, the second ABD binds human CD28 and the VH2 and VL2 are selected from:

[0066] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 9; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 13; or

[0067] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 31; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 35; or

[0068] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 39; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 43; or

[0069] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 47; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 51; or

[0070] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 55; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 59; or

[0071] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 63; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 67; or

[0072] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 86; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 90; or

[0073] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 94; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 98; or

[0074] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 102; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 106; or

[0075] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 110; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 114; or

[0076] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 118; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 122; or

[0077] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 126; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 130; or

[0078] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 134; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 138; or

[0079] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 142; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 146; or

[0080] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 150; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 154; or

[0081] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 158; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 162; or

[0082] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 166; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 170; or

[0083] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 174; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 178; or

[0084] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 182; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 186; or

[0085] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 190; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 194; or

[0086] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 198; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 202; or

[0087] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 380; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 384; or

[0088] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 388; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 392; or

[0089] (i) a VH comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of the VH having the amino acid sequence of SEQ ID NO: 396; and (ii) a VL comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of the VL having the amino acid sequence of SEQ ID NO: 400; or

[0090] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 404; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 408; or

[0091] (i) a VH comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of the VH having the amino acid sequence of SEQ ID NO: 412; and (ii) a VL comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of the VL having the amino acid sequence of SEQ ID NO: 416; or

[0092] (i) VH2 comprising vhCDR1, vhCDR2, and vhCDR3, each having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3 of VH having the amino acid sequence of SEQ ID NO: 420; and (ii) VL2 comprising vlCDR1, vlCDR2, and vlCDR3, each having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3 of VL having the amino acid sequence of SEQ ID NO: 424.

[0093] In certain embodiments, VH2 and VL2 are selected from:

[0094] (i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 10; a vhCDR2 having the amino acid sequence of SEQ ID NO: 11; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 12; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 14; a vlCDR2 having the amino acid sequence of SEQ ID NO: 15; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 16; or

[0095] (i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 32; a vhCDR2 having the amino acid sequence of SEQ ID NO: 33; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 34; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 36; a vlCDR2 having the amino acid sequence of SEQ ID NO: 37; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 38; or

[0096] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 40; a vhCDR2 having the amino acid sequence of SEQ ID NO: 41; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 42; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 44; a vlCDR2 having the amino acid sequence of SEQ ID NO: 45; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 46; or

[0097] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 48; a vhCDR2 having the amino acid sequence of SEQ ID NO: 49; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 50; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 52; a vlCDR2 having the amino acid sequence of SEQ ID NO: 53; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 54; or

[0098] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 56; a vhCDR2 having the amino acid sequence of SEQ ID NO: 57; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 58; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 60; a vlCDR2 having the amino acid sequence of SEQ ID NO: 61; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 62; or

[0099] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 64; a vhCDR2 having the amino acid sequence of SEQ ID NO: 65; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 66; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 68; a vlCDR2 having the amino acid sequence of SEQ ID NO: 69; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 70; or

[0100] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 87; a vhCDR2 having the amino acid sequence of SEQ ID NO: 88; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 89; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 91; a vlCDR2 having the amino acid sequence of SEQ ID NO: 92; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 93; or

[0101] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 95; a vhCDR2 having the amino acid sequence of SEQ ID NO: 96; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 97; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 99; a vlCDR2 having the amino acid sequence of SEQ ID NO: 100; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 101; or

[0102] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 103; a vhCDR2 having the amino acid sequence of SEQ ID NO: 104; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 105; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 107; a vlCDR2 having the amino acid sequence of SEQ ID NO: 108; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 109; or

[0103] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 111; a vhCDR2 having the amino acid sequence of SEQ ID NO: 112; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 113; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 115; a vlCDR2 having the amino acid sequence of SEQ ID NO: 116; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 117; or

[0104] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 119; a vhCDR2 having the amino acid sequence of SEQ ID NO: 120; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 121; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 123; a vlCDR2 having the amino acid sequence of SEQ ID NO: 124; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 125; or

[0105] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 127; a vhCDR2 having the amino acid sequence of SEQ ID NO: 128; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 129; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 131; a vlCDR2 having the amino acid sequence of SEQ ID NO: 132; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 133; or

[0106] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 135; a vhCDR2 having the amino acid sequence of SEQ ID NO: 136; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 137; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 139; a vlCDR2 having the amino acid sequence of SEQ ID NO: 140; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 141; or

[0107] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 143; a vhCDR2 having the amino acid sequence of SEQ ID NO: 144; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 115; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 147; a vlCDR2 having the amino acid sequence of SEQ ID NO: 149; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 149; or

[0108] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 151; a vhCDR2 having the amino acid sequence of SEQ ID NO: 152; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 153; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 155; a vlCDR2 having the amino acid sequence of SEQ ID NO: 156; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 157; or

[0109] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 159; a vhCDR2 having the amino acid sequence of SEQ ID NO: 160; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 161; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 163; a vlCDR2 having the amino acid sequence of SEQ ID NO: 164; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 165; or

[0110] (i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 167; a vhCDR2 having the amino acid sequence of SEQ ID NO: 168; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 169; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 171; a vlCDR2 having the amino acid sequence of SEQ ID NO: 172; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 173; or

[0111] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 175; a vhCDR2 having the amino acid sequence of SEQ ID NO: 176; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 177; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 179; a vlCDR2 having the amino acid sequence of SEQ ID NO: 180; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 181; or

[0112] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 183; a vhCDR2 having the amino acid sequence of SEQ ID NO: 184; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 185; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 187; a vlCDR2 having the amino acid sequence of SEQ ID NO: 188; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 189; or

[0113] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 191; a vhCDR2 having the amino acid sequence of SEQ ID NO: 192; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 193; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 195; a vlCDR2 having the amino acid sequence of SEQ ID NO: 196; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 197; or

[0114] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 199; a vhCDR2 having the amino acid sequence of SEQ ID NO: 200; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 201; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 203; a vlCDR2 having the amino acid sequence of SEQ ID NO: 204; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 205; or

[0115] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 381; a vhCDR2 having the amino acid sequence of SEQ ID NO: 382; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 383; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 385; a vlCDR2 having the amino acid sequence of SEQ ID NO: 386; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 387; or

[0116] (i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 389; a vhCDR2 having the amino acid sequence of SEQ ID NO: 390; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 391; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 393; a vlCDR2 having the amino acid sequence of SEQ ID NO: 394; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 395; or

[0117] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 397; a vhCDR2 having the amino acid sequence of SEQ ID NO: 398; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 399; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 401; a vlCDR2 having the amino acid sequence of SEQ ID NO: 402; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 403; or

[0118] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 405; a vhCDR2 having the amino acid sequence of SEQ ID NO: 406; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 407; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 409; a vlCDR2 having the amino acid sequence of SEQ ID NO: 410; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 411; or

[0119] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 413; a vhCDR2 having the amino acid sequence of SEQ ID NO: 414; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 415; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 417; a vlCDR2 having the amino acid sequence of SEQ ID NO: 418; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 419; or

[0120] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 421; a vhCDR2 having the amino acid sequence of SEQ ID NO: 422; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 423; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 425; a vlCDR2 having the amino acid sequence of SEQ ID NO: 426; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 427.

[0121] In exemplary embodiments, VH2 and VL2 are selected from the following:

[0122] (i) a VH2 having the amino acid sequence of SEQ ID NO: 9; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 13; or

[0123] (i) a VH2 having the amino acid sequence of SEQ ID NO: 31; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 35; or

[0124] (i) a VH2 having the amino acid sequence of SEQ ID NO: 39; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 43; or

[0125] (i) a VH2 having the amino acid sequence of SEQ ID NO: 47; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 51; or

[0126] (i) a VH2 having the amino acid sequence of SEQ ID NO: 55; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 59; or

[0127] (i) a VH2 having the amino acid sequence of SEQ ID NO: 63; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 67; or

[0128] (i) a VH2 having the amino acid sequence of SEQ ID NO: 86; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 90; or

[0129] (i) a VH2 having the amino acid sequence of SEQ ID NO: 94; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 98; or

[0130] (i) a VH2 having the amino acid sequence of SEQ ID NO: 102; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 106; or

[0131] (i) a VH2 having the amino acid sequence of SEQ ID NO: 110; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 114; or

[0132] (i) a VH2 having the amino acid sequence of SEQ ID NO: 118; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 122; or

[0133] (i) a VH2 having the amino acid sequence of SEQ ID NO: 126; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 130; or

[0134] (i) a VH2 having the amino acid sequence of SEQ ID NO: 134; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 138; or

[0135] (i) a VH2 having the amino acid sequence of SEQ ID NO: 142; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 146; or

[0136] (i) a VH2 having the amino acid sequence of SEQ ID NO: 150; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 154; or

[0137] (i) a VH2 having the amino acid sequence of SEQ ID NO: 158; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 162; or

[0138] (i) a VH2 having the amino acid sequence of SEQ ID NO: 166; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 170; or

[0139] (i) a VH2 having the amino acid sequence of SEQ ID NO: 174; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 178; or

[0140] (i) a VH2 having the amino acid sequence of SEQ ID NO: 182; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 186; or

[0141] (i) a VH2 having the amino acid sequence of SEQ ID NO: 190; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 194; or

[0142] (i) a VH2 having the amino acid sequence of SEQ ID NO: 198; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 202; or

[0143] (i) a VH2 having the amino acid sequence of SEQ ID NO: 380; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 384; or

[0144] (i) a VH2 having the amino acid sequence of SEQ ID NO: 388; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 392; or

[0145] (i) a VH2 having the amino acid sequence of SEQ ID NO: 396; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 400; or

[0146] (i) a VH2 having the amino acid sequence of SEQ ID NO: 404; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 408; or

[0147] (i) a VH2 having the amino acid sequence of SEQ ID NO: 412; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 416; or

[0148] (i) a VH2 having the amino acid sequence of SEQ ID NO: 420; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 424.

[0149] In some embodiments, VH1 comprises vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of VH vhCDR1, vhCDR2, and vhCDR3, respectively, having the amino acid sequences of SEQ ID NO: 214; VL1 comprises vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of VL vlCDR1, vlCDR2, and vlCDR3, respectively, having the amino acid sequences of SEQ ID NO: 218; VH2 comprises vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of VH vhCDR1, vhCDR2, and vhCDR3, respectively, having the amino acid sequences of SEQ ID NO: 39; and VL2 comprises vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of VL vlCDR1, vlCDR2, and vlCDR3, respectively, having the amino acid sequences of SEQ ID NO: 43.

[0150] In an exemplary embodiment, VH1 comprises a vhCDR1 having the amino acid sequence of SEQ ID NO: 215; a vhCDR2 having the amino acid sequence of SEQ ID NO: 216; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 217; VL1 comprises a vlCDR1 having the amino acid sequence of SEQ ID NO: 219, a vlCDR2 having the amino acid sequence of SEQ ID NO: 220, and a vlCDR3 having the amino acid sequence of SEQ ID NO: 221; VH2 comprises a vhCDR1 having the amino acid sequence of SEQ ID NO: 40; a vhCDR2 having the amino acid sequence of SEQ ID NO: 41; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 42; and VL2 comprises a vlCDR1 having the amino acid sequence of SEQ ID NO: 44, a vlCDR2 having the amino acid sequence of SEQ ID NO: 45, and a vlCDR3 having the amino acid sequence of SEQ ID NO: 46.

[0151] In some embodiments, the first Fc domain and the second Fc domain are each variant Fc domains. In exemplary embodiments, one of the first and second Fc domains is the heterodimerization variant T366W and the other of the first and second Fc domains comprises the heterodimerization variant T366S / L368A / Y407V, where the numbering is according to EU numbering. In some embodiments, the first Fc domain comprises the heterodimerization variant T366W and the second Fc domain comprises the heterodimerization variant T366S / L368A / Y407V.

[0152] In certain embodiments, the first and second Fc domains each comprise one or more reduced variants, hi some embodiments, the one or more reduced variants comprise L234A / L235A / D265S, where the numbering is according to EU numbering.

[0153] In some embodiments, the first or second Fc domain comprises the purified variant H435R / Y436F, where the numbering is according to EU numbering.

[0154] In an exemplary embodiment, the second Fc domain comprises the purified variant H435R / Y436F.

[0155] In exemplary embodiments, the first Fc domain comprises amino acid substitutions L234A / L235A / D265S / LT366W and the second Fc domain comprises amino acid substitutions L234A / L235A / D265S / T366S / L368A / Y407V / H435R / Y436F, where numbering is according to EU numbering. In some embodiments, the first and second Fc domains each further comprise amino acid substitutions M252Y / S254T / T256E, where numbering is according to EU numbering.

[0156] In some embodiments, the first and second Fc domains comprise a set of heterodimerization variants selected from the following heterodimerization variants: S364K / E357Q:L368D / K370S; S364K:L368D / K370S; S364K:L368E / K370S; D401K:T411E / K360E / Q362E; and T366W:T366S / L368A / Y407V, where numbering is according to EU numbering. In some embodiments, the first and second Fc domains comprise the heterodimerization variant S364K / E357Q:L368D / K370S, where numbering is according to EU numbering.

[0157] In certain embodiments, the first and second Fc domains each comprise one or more reduced variants. In exemplary embodiments, the one or more reduced variants comprise E233P / L234V / L235A / G236del / S267K, where the numbering is according to EU numbering.

[0158] In some embodiments, one of the first or second monomer further comprises a pI variant, in some embodiments, the CH1-hinge-CH2-CH3 of the second monomer comprises the pI variants N208D / Q295E / N384D / Q418E / N421D, where the numbering is according to EU numbering.

[0159] In some embodiments, the CH1-hinge-CH2-CH3 of the second monomer comprises the amino acid variants E233P / L234V / L235A / G236del / S267K / L368D / K370S / N208D / Q295E / N384D / Q418E / N421D and the first Fc domain comprises the amino acid variants E233P / L234V / L235A / G236del / S267K / S364K / E357Q, where numbering is according to EU numbering. In exemplary embodiments, the first and second variant Fc domains each further comprise the amino acid variants 428L / 434S.

[0160] In some embodiments of the anti-CD28 x anti-PSMA antibody, the scFv linker is selected from GKPGSGKPGSGKPGSGKPGS (SEQ ID NO: 443), GGSEGKSSGSGSESKSTGGS (SEQ ID NO: 456), and GGGSGGSGGCPPCGGSGG (SEQ ID NO: 457).

[0161] In a second aspect, provided herein are heterodimeric anti-CD28 x anti-PSMA antibodies in a 2+1 Fab2-scFv-Fc format. These antibodies comprise a) a first monomer; b) a second monomer; and c) a light chain. The first monomer comprises, from N- to C-terminus, VH1-CH1-first domain linker-scFv-second domain linker-CH2-CH3, where VH1 is the first variable heavy domain and CH2-CH3 is the first Fc domain. The second monomer comprises, from N- to C-terminus, VH1-CH1-hinge-CH2-CH3, where CH2-CH3 is the second Fc domain. The light chain comprises, from N- to C-terminus, VL1-CL, where VL1 is the first variable light domain and CL is the constant light domain. The scFv comprises a second VH domain (VH2), an scFv linker, and a second variable light domain (VL2). Each of the VH1 and VL1 together form a first antigen-binding domain (ABD), and VH2 and VL2 form a second ABD. Furthermore, one of the first and second ABDs binds human CD28, and the other of the first and second ABDs binds PSMA.

[0162] In some embodiments, the first ABD binds human CD28 and the second ABD binds PSMA. In certain embodiments, the first ABD binds PSMA and the second ABD binds human CD28.

[0163] In some embodiments, the scFv comprises, from N- to C-terminus, VH2-scFv linker-VL2. In certain embodiments, the scFv comprises, from N- to C-terminus, VL2-scFv linker-VH2.

[0164] In some embodiments, the first ABD binds human PSMA and VH1 and VL1 are selected from:

[0165] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 206; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 210; or

[0166] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 214; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 218; or

[0167] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 222; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 226; or

[0168] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 230; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 234; or

[0169] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 238; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 242; or

[0170] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 246; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 250; or

[0171] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 254; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 258; or

[0172] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 262; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 266; or

[0173] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 270; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 274; or

[0174] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 278; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 282; or

[0175] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 286; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 290; or

[0176] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 294; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 298; or

[0177] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 302; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 306; or

[0178] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 310; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 314; or

[0179] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 318; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 322; or

[0180] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 326; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 330; or

[0181] (i) VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of VH vhCDR1, vhCDR2, and vhCDR3, respectively, having the amino acid sequences of SEQ ID NO: 334; and (ii) VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of VL vlCDR1, vlCDR2, and vlCDR3, respectively, having the amino acid sequences of SEQ ID NO: 338.

[0182] In some embodiments, VH1 and VL1 are selected from:

[0183] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 207; a vhCDR2 having the amino acid sequence of SEQ ID NO: 208; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 209; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 211; a vlCDR2 having the amino acid sequence of SEQ ID NO: 212; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 213; or

[0184] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 215; a vhCDR2 having the amino acid sequence of SEQ ID NO: 216; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 217; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 219; a vlCDR2 having the amino acid sequence of SEQ ID NO: 220; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 221;

[0185] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 223; a vhCDR2 having the amino acid sequence of SEQ ID NO: 224; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 225; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 227; a vlCDR2 having the amino acid sequence of SEQ ID NO: 228; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 229; or

[0186] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 231; a vhCDR2 having the amino acid sequence of SEQ ID NO: 232; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 233; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 235; a vlCDR2 having the amino acid sequence of SEQ ID NO: 236; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 237; or

[0187] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 239; a vhCDR2 having the amino acid sequence of SEQ ID NO: 240; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 241; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 243; a vlCDR2 having the amino acid sequence of SEQ ID NO: 244; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 245; or

[0188] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 247; a vhCDR2 having the amino acid sequence of SEQ ID NO: 248; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 249; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 251; a vlCDR2 having the amino acid sequence of SEQ ID NO: 252; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 253; or

[0189] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 255; a vhCDR2 having the amino acid sequence of SEQ ID NO: 256; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 257; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 259; a vlCDR2 having the amino acid sequence of SEQ ID NO: 260; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 261; or

[0190] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 263; a vhCDR2 having the amino acid sequence of SEQ ID NO: 264; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 265; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 267; a vlCDR2 having the amino acid sequence of SEQ ID NO: 268; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 269; or

[0191] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 271; a vhCDR2 having the amino acid sequence of SEQ ID NO: 212; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 273; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 275; a vlCDR2 having the amino acid sequence of SEQ ID NO: 276; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 277; or

[0192] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 279; a vhCDR2 having the amino acid sequence of SEQ ID NO: 280; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 281; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 283; a vlCDR2 having the amino acid sequence of SEQ ID NO: 284; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 285; or

[0193] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 287; a vhCDR2 having the amino acid sequence of SEQ ID NO: 288; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 289; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 291; a vlCDR2 having the amino acid sequence of SEQ ID NO: 292; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 293; or

[0194] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 295; a vhCDR2 having the amino acid sequence of SEQ ID NO: 296; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 297; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 299; a vlCDR2 having the amino acid sequence of SEQ ID NO: 300; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 301; or

[0195] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 303; a vhCDR2 having the amino acid sequence of SEQ ID NO: 304; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 305; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 307; a vlCDR2 having the amino acid sequence of SEQ ID NO: 308; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 309; or

[0196] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 311; a vhCDR2 having the amino acid sequence of SEQ ID NO: 312; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 313; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 315; a vlCDR2 having the amino acid sequence of SEQ ID NO: 316; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 317; or

[0197] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 319; a vhCDR2 having the amino acid sequence of SEQ ID NO: 320; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 321; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 323; a vlCDR2 having the amino acid sequence of SEQ ID NO: 324; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 325; or

[0198] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 327; a vhCDR2 having the amino acid sequence of SEQ ID NO: 328; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 329; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 331; a vlCDR2 having the amino acid sequence of SEQ ID NO: 332; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 333; or

[0199] (i) VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 335; a vhCDR2 having the amino acid sequence of SEQ ID NO: 336; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 337; and (ii) VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 339; a vlCDR2 having the amino acid sequence of SEQ ID NO: 340; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 341.

[0200] In an exemplary embodiment, VH1 and VL1 are selected from the following:

[0201] (i) a VH1 having the amino acid sequence of SEQ ID NO: 206; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 210; or

[0202] (i) a VH1 having the amino acid sequence of SEQ ID NO: 214; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 218; or

[0203] (i) a VH1 having the amino acid sequence of SEQ ID NO: 222; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 226; or

[0204] (i) a VH1 having the amino acid sequence of SEQ ID NO: 230; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 234; or

[0205] (i) a VH1 having the amino acid sequence of SEQ ID NO: 238; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 242; or

[0206] (i) a VH1 having the amino acid sequence of SEQ ID NO: 246; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 250; or

[0207] (i) a VH1 having the amino acid sequence of SEQ ID NO: 254; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 258; or

[0208] (i) a VH1 having the amino acid sequence of SEQ ID NO: 262; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 266; or

[0209] (i) a VH1 having the amino acid sequence of SEQ ID NO: 270; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 274; or

[0210] (i) a VH1 having the amino acid sequence of SEQ ID NO: 278; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 282; or

[0211] (i) a VH1 having the amino acid sequence of SEQ ID NO: 286; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 290; or

[0212] (i) a VH1 having the amino acid sequence of SEQ ID NO: 294; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 298; or

[0213] (i) a VH1 having the amino acid sequence of SEQ ID NO: 302; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 306; or

[0214] (i) a VH1 having the amino acid sequence of SEQ ID NO: 310; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 314; or

[0215] (i) a VH1 having the amino acid sequence of SEQ ID NO: 318; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 322; or

[0216] (i) a VH1 having the amino acid sequence of SEQ ID NO: 326; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 330; or

[0217] (i) VH1 having the amino acid sequence of SEQ ID NO: 334; and (ii) VL1 having the amino acid sequence of SEQ ID NO: 338.

[0218] In some embodiments, the second ABD binds human CD28 and the VH2 and VL2 are selected from:

[0219] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 9; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 13; or

[0220] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 31; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 35; or

[0221] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 39; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 43; or

[0222] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 47; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 51; or

[0223] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 55; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 59; or

[0224] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 63; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 67; or

[0225] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 86; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 90; or

[0226] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 94; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 98; or

[0227] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 102; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 106; or

[0228] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 110; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 114; or

[0229] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 118; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 122; or

[0230] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 126; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 130; or

[0231] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 134; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 138; or

[0232] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 142; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 146; or

[0233] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 150; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 154; or

[0234] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 158; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 162; or

[0235] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 166; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 170; or

[0236] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 174; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 178; or

[0237] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 182; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 186; or

[0238] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 190; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 194; or

[0239] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 198; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 202; or

[0240] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 380; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 384; or

[0241] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 388; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 392; or

[0242] (i) a VH comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of the VH having the amino acid sequence of SEQ ID NO: 396; and (ii) a VL comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of the VL having the amino acid sequence of SEQ ID NO: 400; or

[0243] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 404; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 408; or

[0244] (i) a VH comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of the VH having the amino acid sequence of SEQ ID NO: 412; and (ii) a VL comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of the VL having the amino acid sequence of SEQ ID NO: 416; or

[0245] (i) VH2 comprising vhCDR1, vhCDR2, and vhCDR3, each having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3 of VH having the amino acid sequence of SEQ ID NO: 420; and (ii) VL2 comprising vlCDR1, vlCDR2, and vlCDR3, each having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3 of VL having the amino acid sequence of SEQ ID NO: 424.

[0246] In certain embodiments, VH2 and VL2 are selected from:

[0247] (i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 10; a vhCDR2 having the amino acid sequence of SEQ ID NO: 11; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 12; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 14; a vlCDR2 having the amino acid sequence of SEQ ID NO: 15; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 16; or

[0248] (i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 32; a vhCDR2 having the amino acid sequence of SEQ ID NO: 33; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 34; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 36; a vlCDR2 having the amino acid sequence of SEQ ID NO: 37; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 38; or

[0249] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 40; a vhCDR2 having the amino acid sequence of SEQ ID NO: 41; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 42; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 44; a vlCDR2 having the amino acid sequence of SEQ ID NO: 45; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 46; or

[0250] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 48; a vhCDR2 having the amino acid sequence of SEQ ID NO: 49; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 50; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 52; a vlCDR2 having the amino acid sequence of SEQ ID NO: 53; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 54; or

[0251] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 56; a vhCDR2 having the amino acid sequence of SEQ ID NO: 57; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 58; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 60; a vlCDR2 having the amino acid sequence of SEQ ID NO: 61; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 62; or

[0252] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 64; a vhCDR2 having the amino acid sequence of SEQ ID NO: 65; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 66; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 68; a vlCDR2 having the amino acid sequence of SEQ ID NO: 69; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 70; or

[0253] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 87; a vhCDR2 having the amino acid sequence of SEQ ID NO: 88; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 89; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 91; a vlCDR2 having the amino acid sequence of SEQ ID NO: 92; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 93; or

[0254] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 95; a vhCDR2 having the amino acid sequence of SEQ ID NO: 96; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 97; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 99; a vlCDR2 having the amino acid sequence of SEQ ID NO: 100; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 101; or

[0255] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 103; a vhCDR2 having the amino acid sequence of SEQ ID NO: 104; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 105; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 107; a vlCDR2 having the amino acid sequence of SEQ ID NO: 108; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 109; or

[0256] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 111; a vhCDR2 having the amino acid sequence of SEQ ID NO: 112; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 113; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 115; a vlCDR2 having the amino acid sequence of SEQ ID NO: 116; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 117; or

[0257] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 119; a vhCDR2 having the amino acid sequence of SEQ ID NO: 120; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 121; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 123; a vlCDR2 having the amino acid sequence of SEQ ID NO: 124; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 125; or

[0258] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 127; a vhCDR2 having the amino acid sequence of SEQ ID NO: 128; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 129; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 131; a vlCDR2 having the amino acid sequence of SEQ ID NO: 132; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 133; or

[0259] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 135; a vhCDR2 having the amino acid sequence of SEQ ID NO: 136; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 137; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 139; a vlCDR2 having the amino acid sequence of SEQ ID NO: 140; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 141; or

[0260] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 143; a vhCDR2 having the amino acid sequence of SEQ ID NO: 144; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 115; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 147; a vlCDR2 having the amino acid sequence of SEQ ID NO: 149; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 149; or

[0261] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 151; a vhCDR2 having the amino acid sequence of SEQ ID NO: 152; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 153; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 155; a vlCDR2 having the amino acid sequence of SEQ ID NO: 156; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 157; or

[0262] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 159; a vhCDR2 having the amino acid sequence of SEQ ID NO: 160; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 161; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 163; a vlCDR2 having the amino acid sequence of SEQ ID NO: 164; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 165; or

[0263] (i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 167; a vhCDR2 having the amino acid sequence of SEQ ID NO: 168; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 169; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 171; a vlCDR2 having the amino acid sequence of SEQ ID NO: 172; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 173; or

[0264] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 175; a vhCDR2 having the amino acid sequence of SEQ ID NO: 176; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 177; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 179; a vlCDR2 having the amino acid sequence of SEQ ID NO: 180; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 181; or

[0265] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 183; a vhCDR2 having the amino acid sequence of SEQ ID NO: 184; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 185; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 187; a vlCDR2 having the amino acid sequence of SEQ ID NO: 188; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 189; or

[0266] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 191; a vhCDR2 having the amino acid sequence of SEQ ID NO: 192; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 193; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 195; a vlCDR2 having the amino acid sequence of SEQ ID NO: 196; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 197; or

[0267] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 199; a vhCDR2 having the amino acid sequence of SEQ ID NO: 200; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 201; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 203; a vlCDR2 having the amino acid sequence of SEQ ID NO: 204; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 205; or

[0268] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 381; a vhCDR2 having the amino acid sequence of SEQ ID NO: 382; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 383; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 385; a vlCDR2 having the amino acid sequence of SEQ ID NO: 386; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 387; or

[0269] (i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 389; a vhCDR2 having the amino acid sequence of SEQ ID NO: 390; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 391; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 393; a vlCDR2 having the amino acid sequence of SEQ ID NO: 394; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 395; or

[0270] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 397; a vhCDR2 having the amino acid sequence of SEQ ID NO: 398; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 399; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 401; a vlCDR2 having the amino acid sequence of SEQ ID NO: 402; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 403; or

[0271] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 405; a vhCDR2 having the amino acid sequence of SEQ ID NO: 406; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 407; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 409; a vlCDR2 having the amino acid sequence of SEQ ID NO: 410; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 411; or

[0272] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 413; a vhCDR2 having the amino acid sequence of SEQ ID NO: 414; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 415; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 417; a vlCDR2 having the amino acid sequence of SEQ ID NO: 418; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 419; or

[0273] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 421; a vhCDR2 having the amino acid sequence of SEQ ID NO: 422; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 423; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 425; a vlCDR2 having the amino acid sequence of SEQ ID NO: 426; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 427.

[0274] In exemplary embodiments, VH2 and VL2 are selected from the following:

[0275] (i) a VH2 having the amino acid sequence of SEQ ID NO: 9; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 13; or

[0276] (i) a VH2 having the amino acid sequence of SEQ ID NO: 31; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 35; or

[0277] (i) a VH2 having the amino acid sequence of SEQ ID NO: 39; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 43; or

[0278] (i) a VH2 having the amino acid sequence of SEQ ID NO: 47; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 51; or

[0279] (i) a VH2 having the amino acid sequence of SEQ ID NO: 55; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 59; or

[0280] (i) a VH2 having the amino acid sequence of SEQ ID NO: 63; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 67; or

[0281] (i) a VH2 having the amino acid sequence of SEQ ID NO: 86; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 90; or

[0282] (i) a VH2 having the amino acid sequence of SEQ ID NO: 94; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 98; or

[0283] (i) a VH2 having the amino acid sequence of SEQ ID NO: 102; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 106; or

[0284] (i) a VH2 having the amino acid sequence of SEQ ID NO: 110; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 114; or

[0285] (i) a VH2 having the amino acid sequence of SEQ ID NO: 118; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 122; or

[0286] (i) a VH2 having the amino acid sequence of SEQ ID NO: 126; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 130; or

[0287] (i) a VH2 having the amino acid sequence of SEQ ID NO: 134; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 138; or

[0288] (i) a VH2 having the amino acid sequence of SEQ ID NO: 142; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 146; or

[0289] (i) a VH2 having the amino acid sequence of SEQ ID NO: 150; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 154; or

[0290] (i) a VH2 having the amino acid sequence of SEQ ID NO: 158; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 162; or

[0291] (i) a VH2 having the amino acid sequence of SEQ ID NO: 166; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 170; or

[0292] (i) a VH2 having the amino acid sequence of SEQ ID NO: 174; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 178; or

[0293] (i) a VH2 having the amino acid sequence of SEQ ID NO: 182; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 186; or

[0294] (i) a VH2 having the amino acid sequence of SEQ ID NO: 190; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 194; or

[0295] (i) a VH2 having the amino acid sequence of SEQ ID NO: 198; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 202; or

[0296] (i) a VH2 having the amino acid sequence of SEQ ID NO: 380; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 384; or

[0297] (i) a VH2 having the amino acid sequence of SEQ ID NO: 388; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 392; or

[0298] (i) a VH2 having the amino acid sequence of SEQ ID NO: 396; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 400; or

[0299] (i) a VH2 having the amino acid sequence of SEQ ID NO: 404; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 408; or

[0300] (i) a VH2 having the amino acid sequence of SEQ ID NO: 412; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 416; or

[0301] (i) a VH2 having the amino acid sequence of SEQ ID NO: 420; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 424.

[0302] In some embodiments, VH1 comprises vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of VH vhCDR1, vhCDR2, and vhCDR3, respectively, having the amino acid sequences of SEQ ID NO: 214; VL1 comprises vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of VL vlCDR1, vlCDR2, and vlCDR3, respectively, having the amino acid sequences of SEQ ID NO: 218; VH2 comprises vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of VH vhCDR1, vhCDR2, and vhCDR3, respectively, having the amino acid sequences of SEQ ID NO: 39; and VL2 comprises vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of VL vlCDR1, vlCDR2, and vlCDR3, respectively, having the amino acid sequences of SEQ ID NO: 43.

[0303] In an exemplary embodiment, VH1 comprises a vhCDR1 having the amino acid sequence of SEQ ID NO: 215; a vhCDR2 having the amino acid sequence of SEQ ID NO: 216; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 217; VL1 comprises a vlCDR1 having the amino acid sequence of SEQ ID NO: 219, a vlCDR2 having the amino acid sequence of SEQ ID NO: 220, and a vlCDR3 having the amino acid sequence of SEQ ID NO: 221; VH2 comprises a vhCDR1 having the amino acid sequence of SEQ ID NO: 40; a vhCDR2 having the amino acid sequence of SEQ ID NO: 41; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 42; and VL2 comprises a vlCDR1 having the amino acid sequence of SEQ ID NO: 44, a vlCDR2 having the amino acid sequence of SEQ ID NO: 45, and a vlCDR3 having the amino acid sequence of SEQ ID NO: 46.

[0304] In some embodiments, the first Fc domain and the second Fc domain are each variant Fc domains. In exemplary embodiments, one of the first and second Fc domains is the heterodimerization variant T366W and the other of the first and second Fc domains comprises the heterodimerization variant T366S / L368A / Y407V, where the numbering is according to EU numbering. In some embodiments, the first Fc domain comprises the heterodimerization variant T366W and the second Fc domain comprises the heterodimerization variant T366S / L368A / Y407V.

[0305] In certain embodiments, the first and second Fc domains each comprise one or more reduced variants, hi some embodiments, the one or more reduced variants comprise L234A / L235A / D265S, where the numbering is according to EU numbering.

[0306] In some embodiments, the first or second Fc domain comprises the purified variant H435R / Y436F, where the numbering is according to EU numbering.

[0307] In an exemplary embodiment, the second Fc domain comprises the purified variant H435R / Y436F.

[0308] In exemplary embodiments, the first Fc domain comprises amino acid substitutions L234A / L235A / D265S / LT366W and the second Fc domain comprises amino acid substitutions L234A / L235A / D265S / T366S / L368A / Y407V / H435R / Y436F, where numbering is according to EU numbering. In some embodiments, the first and second Fc domains each further comprise amino acid substitutions M252Y / S254T / T256E, where numbering is according to EU numbering.

[0309] In some embodiments, the first and second Fc domains comprise a set of heterodimerization variants selected from the following heterodimerization variants: S364K / E357Q:L368D / K370S; S364K:L368D / K370S; S364K:L368E / K370S; D401K:T411E / K360E / Q362E; and T366W:T366S / L368A / Y407V, where numbering is according to EU numbering. In some embodiments, the first and second Fc domains comprise the heterodimerization variant S364K / E357Q:L368D / K370S, where numbering is according to EU numbering.

[0310] In certain embodiments, the first and second Fc domains each comprise one or more reduced variants. In exemplary embodiments, the one or more reduced variants comprise E233P / L234V / L235A / G236del / S267K, where the numbering is according to EU numbering.

[0311] In some embodiments, one of the first or second monomer further comprises a pI variant, in some embodiments, the CH1-hinge-CH2-CH3 of the second monomer comprises the pI variants N208D / Q295E / N384D / Q418E / N421D, where the numbering is according to EU numbering.

[0312] In some embodiments, the CH1-hinge-CH2-CH3 of the second monomer comprises the amino acid variants E233P / L234V / L235A / G236del / S267K / L368D / K370S / N208D / Q295E / N384D / Q418E / N421D and the first Fc domain comprises the amino acid variants E233P / L234V / L235A / G236del / S267K / S364K / E357Q, where numbering is according to EU numbering. In exemplary embodiments, the first and second variant Fc domains each further comprise the amino acid variants 428L / 434S.

[0313] In some embodiments of the anti-CD28 x anti-PSMA antibody, the scFv linker is selected from GKPGSGKPGSGKPGSGKPGS (SEQ ID NO: 443), GGSEGKSSGSGSESKSTGGS (SEQ ID NO: 456), and GGGSGGSGGCPPCGGSGG (SEQ ID NO: 457).

[0314] In another aspect, provided herein are heterodimeric anti-CD28 x anti-PSMA antibodies in a 2+1 mAb-scFv format. These antibodies comprise: a) a first monomer; b) a second monomer; and c) a light chain. The first monomer comprises, from N- to C-terminus, VH1-CH1-hinge-CH2-CH3-domain linker-scFv, where VH1 is the first variable heavy domain and CH2-CH3 are the first Fc domain. The second monomer comprises, from N- to C-terminus, VH1-CH1-hinge-CH2-CH3, where VH1 is the first variable heavy domain and CH2-CH3 are the second Fc domain. The light chain comprises, from N- to C-terminus, VL1-CL, where VL1 is the first variable light domain and CL is the constant light domain. The scFv comprises a second VH domain (VH2), an scFv linker, and a second variable light domain (VL2). Each of the VH1 and VL1 together form a first antigen-binding domain (ABD), and VH2 and VL2 form a second ABD. Furthermore, one of the first and second ABDs binds human CD28, and the other of the first and second ABDs binds PSMA.

[0315] In some embodiments, the first ABD binds human CD28 and the second ABD binds PSMA. In certain embodiments, the first ABD binds PSMA and the second ABD binds human CD28.

[0316] In some embodiments, the scFv comprises, from N- to C-terminus, VH2-scFv linker-VL2. In certain embodiments, the scFv comprises, from N- to C-terminus, VL2-scFv linker-VH2.

[0317] In some embodiments, the first ABD binds human PSMA and VH1 and VL1 are selected from:

[0318] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 206; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 210; or

[0319] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 214; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 218; or

[0320] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 222; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 226; or

[0321] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 230; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 234; or

[0322] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 238; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 242; or

[0323] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 246; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 250; or

[0324] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 254; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 258; or

[0325] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 262; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 266; or

[0326] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 270; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 274; or

[0327] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 278; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 282; or

[0328] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 286; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 290; or

[0329] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 294; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 298; or

[0330] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 302; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 306; or

[0331] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 310; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 314; or

[0332] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 318; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 322; or

[0333] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 326; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 330; or

[0334] (i) VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of VH vhCDR1, vhCDR2, and vhCDR3, respectively, having the amino acid sequences of SEQ ID NO: 334; and (ii) VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of VL vlCDR1, vlCDR2, and vlCDR3, respectively, having the amino acid sequences of SEQ ID NO: 338.

[0335] In some embodiments, VH1 and VL1 are selected from:

[0336] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 207; a vhCDR2 having the amino acid sequence of SEQ ID NO: 208; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 209; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 211; a vlCDR2 having the amino acid sequence of SEQ ID NO: 212; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 213; or

[0337] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 215; a vhCDR2 having the amino acid sequence of SEQ ID NO: 216; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 217; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 219; a vlCDR2 having the amino acid sequence of SEQ ID NO: 220; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 221;

[0338] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 223; a vhCDR2 having the amino acid sequence of SEQ ID NO: 224; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 225; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 227; a vlCDR2 having the amino acid sequence of SEQ ID NO: 228; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 229; or

[0339] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 231; a vhCDR2 having the amino acid sequence of SEQ ID NO: 232; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 233; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 235; a vlCDR2 having the amino acid sequence of SEQ ID NO: 236; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 237; or

[0340] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 239; a vhCDR2 having the amino acid sequence of SEQ ID NO: 240; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 241; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 243; a vlCDR2 having the amino acid sequence of SEQ ID NO: 244; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 245; or

[0341] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 247; a vhCDR2 having the amino acid sequence of SEQ ID NO: 248; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 249; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 251; a vlCDR2 having the amino acid sequence of SEQ ID NO: 252; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 253; or

[0342] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 255; a vhCDR2 having the amino acid sequence of SEQ ID NO: 256; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 257; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 259; a vlCDR2 having the amino acid sequence of SEQ ID NO: 260; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 261; or

[0343] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 263; a vhCDR2 having the amino acid sequence of SEQ ID NO: 264; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 265; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 267; a vlCDR2 having the amino acid sequence of SEQ ID NO: 268; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 269; or

[0344] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 271; a vhCDR2 having the amino acid sequence of SEQ ID NO: 212; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 273; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 275; a vlCDR2 having the amino acid sequence of SEQ ID NO: 276; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 277; or

[0345] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 279; a vhCDR2 having the amino acid sequence of SEQ ID NO: 280; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 281; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 283; a vlCDR2 having the amino acid sequence of SEQ ID NO: 284; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 285; or

[0346] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 287; a vhCDR2 having the amino acid sequence of SEQ ID NO: 288; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 289; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 291; a vlCDR2 having the amino acid sequence of SEQ ID NO: 292; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 293; or

[0347] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 295; a vhCDR2 having the amino acid sequence of SEQ ID NO: 296; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 297; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 299; a vlCDR2 having the amino acid sequence of SEQ ID NO: 300; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 301; or

[0348] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 303; a vhCDR2 having the amino acid sequence of SEQ ID NO: 304; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 305; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 307; a vlCDR2 having the amino acid sequence of SEQ ID NO: 308; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 309; or

[0349] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 311; a vhCDR2 having the amino acid sequence of SEQ ID NO: 312; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 313; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 315; a vlCDR2 having the amino acid sequence of SEQ ID NO: 316; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 317; or

[0350] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 319; a vhCDR2 having the amino acid sequence of SEQ ID NO: 320; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 321; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 323; a vlCDR2 having the amino acid sequence of SEQ ID NO: 324; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 325; or

[0351] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 327; a vhCDR2 having the amino acid sequence of SEQ ID NO: 328; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 329; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 331; a vlCDR2 having the amino acid sequence of SEQ ID NO: 332; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 333; or

[0352] (i) VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 335; a vhCDR2 having the amino acid sequence of SEQ ID NO: 336; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 337; and (ii) VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 339; a vlCDR2 having the amino acid sequence of SEQ ID NO: 340; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 341.

[0353] In an exemplary embodiment, VH1 and VL1 are selected from the following:

[0354] (i) a VH1 having the amino acid sequence of SEQ ID NO: 206; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 210; or

[0355] (i) a VH1 having the amino acid sequence of SEQ ID NO: 214; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 218; or

[0356] (i) a VH1 having the amino acid sequence of SEQ ID NO: 222; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 226; or

[0357] (i) a VH1 having the amino acid sequence of SEQ ID NO: 230; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 234; or

[0358] (i) a VH1 having the amino acid sequence of SEQ ID NO: 238; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 242; or

[0359] (i) a VH1 having the amino acid sequence of SEQ ID NO: 246; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 250; or

[0360] (i) a VH1 having the amino acid sequence of SEQ ID NO: 254; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 258; or

[0361] (i) a VH1 having the amino acid sequence of SEQ ID NO: 262; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 266; or

[0362] (i) a VH1 having the amino acid sequence of SEQ ID NO: 270; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 274; or

[0363] (i) a VH1 having the amino acid sequence of SEQ ID NO: 278; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 282; or

[0364] (i) a VH1 having the amino acid sequence of SEQ ID NO: 286; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 290; or

[0365] (i) a VH1 having the amino acid sequence of SEQ ID NO: 294; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 298; or

[0366] (i) a VH1 having the amino acid sequence of SEQ ID NO: 302; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 306; or

[0367] (i) a VH1 having the amino acid sequence of SEQ ID NO: 310; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 314; or

[0368] (i) a VH1 having the amino acid sequence of SEQ ID NO: 318; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 322; or

[0369] (i) a VH1 having the amino acid sequence of SEQ ID NO: 326; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 330; or

[0370] (i) VH1 having the amino acid sequence of SEQ ID NO: 334; and (ii) VL1 having the amino acid sequence of SEQ ID NO: 338.

[0371] In some embodiments, the second ABD binds human CD28 and the VH2 and VL2 are selected from:

[0372] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 9; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 13; or

[0373] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 31; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 35; or

[0374] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 39; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 43; or

[0375] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 47; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 51; or

[0376] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 55; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 59; or

[0377] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 63; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 67; or

[0378] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 86; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 90; or

[0379] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 94; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 98; or

[0380] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 102; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 106; or

[0381] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 110; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 114; or

[0382] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 118; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 122; or

[0383] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 126; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 130; or

[0384] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 134; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 138; or

[0385] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 142; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 146; or

[0386] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 150; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 154; or

[0387] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 158; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 162; or

[0388] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 166; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 170; or

[0389] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 174; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 178; or

[0390] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 182; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 186; or

[0391] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 190; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 194; or

[0392] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 198; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 202; or

[0393] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 380; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 384; or

[0394] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 388; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 392; or

[0395] (i) a VH comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of the VH having the amino acid sequence of SEQ ID NO: 396; and (ii) a VL comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of the VL having the amino acid sequence of SEQ ID NO: 400; or

[0396] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 404; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 408; or

[0397] (i) a VH comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of the VH having the amino acid sequence of SEQ ID NO: 412; and (ii) a VL comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of the VL having the amino acid sequence of SEQ ID NO: 416; or

[0398] (i) VH2 comprising vhCDR1, vhCDR2, and vhCDR3, each having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3 of VH having the amino acid sequence of SEQ ID NO: 420; and (ii) VL2 comprising vlCDR1, vlCDR2, and vlCDR3, each having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3 of VL having the amino acid sequence of SEQ ID NO: 424.

[0399] In certain embodiments, VH2 and VL2 are selected from:

[0400] (i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 10; a vhCDR2 having the amino acid sequence of SEQ ID NO: 11; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 12; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 14; a vlCDR2 having the amino acid sequence of SEQ ID NO: 15; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 16; or

[0401] (i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 32; a vhCDR2 having the amino acid sequence of SEQ ID NO: 33; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 34; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 36; a vlCDR2 having the amino acid sequence of SEQ ID NO: 37; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 38; or

[0402] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 40; a vhCDR2 having the amino acid sequence of SEQ ID NO: 41; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 42; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 44; a vlCDR2 having the amino acid sequence of SEQ ID NO: 45; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 46; or

[0403] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 48; a vhCDR2 having the amino acid sequence of SEQ ID NO: 49; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 50; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 52; a vlCDR2 having the amino acid sequence of SEQ ID NO: 53; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 54; or

[0404] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 56; a vhCDR2 having the amino acid sequence of SEQ ID NO: 57; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 58; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 60; a vlCDR2 having the amino acid sequence of SEQ ID NO: 61; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 62; or

[0405] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 64; a vhCDR2 having the amino acid sequence of SEQ ID NO: 65; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 66; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 68; a vlCDR2 having the amino acid sequence of SEQ ID NO: 69; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 70; or

[0406] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 87; a vhCDR2 having the amino acid sequence of SEQ ID NO: 88; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 89; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 91; a vlCDR2 having the amino acid sequence of SEQ ID NO: 92; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 93; or

[0407] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 95; a vhCDR2 having the amino acid sequence of SEQ ID NO: 96; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 97; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 99; a vlCDR2 having the amino acid sequence of SEQ ID NO: 100; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 101; or

[0408] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 103; a vhCDR2 having the amino acid sequence of SEQ ID NO: 104; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 105; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 107; a vlCDR2 having the amino acid sequence of SEQ ID NO: 108; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 109; or

[0409] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 111; a vhCDR2 having the amino acid sequence of SEQ ID NO: 112; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 113; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 115; a vlCDR2 having the amino acid sequence of SEQ ID NO: 116; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 117; or

[0410] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 119; a vhCDR2 having the amino acid sequence of SEQ ID NO: 120; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 121; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 123; a vlCDR2 having the amino acid sequence of SEQ ID NO: 124; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 125; or

[0411] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 127; a vhCDR2 having the amino acid sequence of SEQ ID NO: 128; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 129; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 131; a vlCDR2 having the amino acid sequence of SEQ ID NO: 132; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 133; or

[0412] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 135; a vhCDR2 having the amino acid sequence of SEQ ID NO: 136; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 137; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 139; a vlCDR2 having the amino acid sequence of SEQ ID NO: 140; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 141; or

[0413] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 143; a vhCDR2 having the amino acid sequence of SEQ ID NO: 144; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 115; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 147; a vlCDR2 having the amino acid sequence of SEQ ID NO: 149; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 149; or

[0414] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 151; a vhCDR2 having the amino acid sequence of SEQ ID NO: 152; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 153; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 155; a vlCDR2 having the amino acid sequence of SEQ ID NO: 156; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 157; or

[0415] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 159; a vhCDR2 having the amino acid sequence of SEQ ID NO: 160; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 161; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 163; a vlCDR2 having the amino acid sequence of SEQ ID NO: 164; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 165; or

[0416] (i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 167; a vhCDR2 having the amino acid sequence of SEQ ID NO: 168; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 169; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 171; a vlCDR2 having the amino acid sequence of SEQ ID NO: 172; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 173; or

[0417] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 175; a vhCDR2 having the amino acid sequence of SEQ ID NO: 176; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 177; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 179; a vlCDR2 having the amino acid sequence of SEQ ID NO: 180; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 181; or

[0418] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 183; a vhCDR2 having the amino acid sequence of SEQ ID NO: 184; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 185; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 187; a vlCDR2 having the amino acid sequence of SEQ ID NO: 188; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 189; or

[0419] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 191; a vhCDR2 having the amino acid sequence of SEQ ID NO: 192; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 193; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 195; a vlCDR2 having the amino acid sequence of SEQ ID NO: 196; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 197; or

[0420] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 199; a vhCDR2 having the amino acid sequence of SEQ ID NO: 200; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 201; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 203; a vlCDR2 having the amino acid sequence of SEQ ID NO: 204; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 205; or

[0421] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 381; a vhCDR2 having the amino acid sequence of SEQ ID NO: 382; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 383; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 385; a vlCDR2 having the amino acid sequence of SEQ ID NO: 386; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 387; or

[0422] (i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 389; a vhCDR2 having the amino acid sequence of SEQ ID NO: 390; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 391; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 393; a vlCDR2 having the amino acid sequence of SEQ ID NO: 394; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 395; or

[0423] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 397; a vhCDR2 having the amino acid sequence of SEQ ID NO: 398; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 399; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 401; a vlCDR2 having the amino acid sequence of SEQ ID NO: 402; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 403; or

[0424] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 405; a vhCDR2 having the amino acid sequence of SEQ ID NO: 406; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 407; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 409; a vlCDR2 having the amino acid sequence of SEQ ID NO: 410; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 411; or

[0425] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 413; a vhCDR2 having the amino acid sequence of SEQ ID NO: 414; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 415; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 417; a vlCDR2 having the amino acid sequence of SEQ ID NO: 418; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 419; or

[0426] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 421; a vhCDR2 having the amino acid sequence of SEQ ID NO: 422; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 423; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 425; a vlCDR2 having the amino acid sequence of SEQ ID NO: 426; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 427.

[0427] In exemplary embodiments, VH2 and VL2 are selected from the following:

[0428] (i) a VH2 having the amino acid sequence of SEQ ID NO: 9; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 13; or

[0429] (i) a VH2 having the amino acid sequence of SEQ ID NO: 31; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 35; or

[0430] (i) a VH2 having the amino acid sequence of SEQ ID NO: 39; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 43; or

[0431] (i) a VH2 having the amino acid sequence of SEQ ID NO: 47; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 51; or

[0432] (i) a VH2 having the amino acid sequence of SEQ ID NO: 55; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 59; or

[0433] (i) a VH2 having the amino acid sequence of SEQ ID NO: 63; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 67; or

[0434] (i) a VH2 having the amino acid sequence of SEQ ID NO: 86; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 90; or

[0435] (i) a VH2 having the amino acid sequence of SEQ ID NO: 94; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 98; or

[0436] (i) a VH2 having the amino acid sequence of SEQ ID NO: 102; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 106; or

[0437] (i) a VH2 having the amino acid sequence of SEQ ID NO: 110; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 114; or

[0438] (i) a VH2 having the amino acid sequence of SEQ ID NO: 118; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 122; or

[0439] (i) a VH2 having the amino acid sequence of SEQ ID NO: 126; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 130; or

[0440] (i) a VH2 having the amino acid sequence of SEQ ID NO: 134; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 138; or

[0441] (i) a VH2 having the amino acid sequence of SEQ ID NO: 142; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 146; or

[0442] (i) a VH2 having the amino acid sequence of SEQ ID NO: 150; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 154; or

[0443] (i) a VH2 having the amino acid sequence of SEQ ID NO: 158; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 162; or

[0444] (i) a VH2 having the amino acid sequence of SEQ ID NO: 166; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 170; or

[0445] (i) a VH2 having the amino acid sequence of SEQ ID NO: 174; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 178; or

[0446] (i) a VH2 having the amino acid sequence of SEQ ID NO: 182; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 186; or

[0447] (i) a VH2 having the amino acid sequence of SEQ ID NO: 190; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 194; or

[0448] (i) a VH2 having the amino acid sequence of SEQ ID NO: 198; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 202; or

[0449] (i) a VH2 having the amino acid sequence of SEQ ID NO: 380; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 384; or

[0450] (i) a VH2 having the amino acid sequence of SEQ ID NO: 388; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 392; or

[0451] (i) a VH2 having the amino acid sequence of SEQ ID NO: 396; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 400; or

[0452] (i) a VH2 having the amino acid sequence of SEQ ID NO: 404; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 408; or

[0453] (i) a VH2 having the amino acid sequence of SEQ ID NO: 412; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 416; or

[0454] (i) a VH2 having the amino acid sequence of SEQ ID NO: 420; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 424.

[0455] In some embodiments, VH1 comprises vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of VH vhCDR1, vhCDR2, and vhCDR3, respectively, having the amino acid sequences of SEQ ID NO: 214; VL1 comprises vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of VL vlCDR1, vlCDR2, and vlCDR3, respectively, having the amino acid sequences of SEQ ID NO: 218; VH2 comprises vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of VH vhCDR1, vhCDR2, and vhCDR3, respectively, having the amino acid sequences of SEQ ID NO: 39; and VL2 comprises vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of VL vlCDR1, vlCDR2, and vlCDR3, respectively, having the amino acid sequences of SEQ ID NO: 43.

[0456] In an exemplary embodiment, VH1 comprises a vhCDR1 having the amino acid sequence of SEQ ID NO: 215; a vhCDR2 having the amino acid sequence of SEQ ID NO: 216; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 217; VL1 comprises a vlCDR1 having the amino acid sequence of SEQ ID NO: 219, a vlCDR2 having the amino acid sequence of SEQ ID NO: 220, and a vlCDR3 having the amino acid sequence of SEQ ID NO: 221; VH2 comprises a vhCDR1 having the amino acid sequence of SEQ ID NO: 40; a vhCDR2 having the amino acid sequence of SEQ ID NO: 41; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 42; and VL2 comprises a vlCDR1 having the amino acid sequence of SEQ ID NO: 44, a vlCDR2 having the amino acid sequence of SEQ ID NO: 45, and a vlCDR3 having the amino acid sequence of SEQ ID NO: 46.

[0457] In some embodiments, the first Fc domain and the second Fc domain are each variant Fc domains. In exemplary embodiments, one of the first and second Fc domains is the heterodimerization variant T366W and the other of the first and second Fc domains comprises the heterodimerization variant T366S / L368A / Y407V, where the numbering is according to EU numbering. In some embodiments, the first Fc domain comprises the heterodimerization variant T366W and the second Fc domain comprises the heterodimerization variant T366S / L368A / Y407V.

[0458] In certain embodiments, the first and second Fc domains each comprise one or more reduced variants, hi some embodiments, the one or more reduced variants comprise L234A / L235A / D265S, where the numbering is according to EU numbering.

[0459] In some embodiments, the first or second Fc domain comprises the purified variant H435R / Y436F, where the numbering is according to EU numbering.

[0460] In an exemplary embodiment, the second Fc domain comprises the purified variant H435R / Y436F.

[0461] In exemplary embodiments, the first Fc domain comprises amino acid substitutions L234A / L235A / D265S / LT366W and the second Fc domain comprises amino acid substitutions L234A / L235A / D265S / T366S / L368A / Y407V / H435R / Y436F, where numbering is according to EU numbering. In some embodiments, the first and second Fc domains each further comprise amino acid substitutions M252Y / S254T / T256E, where numbering is according to EU numbering.

[0462] In some embodiments, the first and second Fc domains comprise a set of heterodimerization variants selected from the following heterodimerization variants: S364K / E357Q:L368D / K370S; S364K:L368D / K370S; S364K:L368E / K370S; D401K:T411E / K360E / Q362E; and T366W:T366S / L368A / Y407V, where numbering is according to EU numbering. In some embodiments, the first and second Fc domains comprise the heterodimerization variant S364K / E357Q:L368D / K370S, where numbering is according to EU numbering.

[0463] In certain embodiments, the first and second Fc domains each comprise one or more reduced variants. In exemplary embodiments, the one or more reduced variants comprise E233P / L234V / L235A / G236del / S267K, where the numbering is according to EU numbering.

[0464] In some embodiments, one of the first or second monomer further comprises a pI variant, in some embodiments, the CH1-hinge-CH2-CH3 of the second monomer comprises the pI variants N208D / Q295E / N384D / Q418E / N421D, where the numbering is according to EU numbering.

[0465] In some embodiments, the CH1-hinge-CH2-CH3 of the second monomer comprises the amino acid variants E233P / L234V / L235A / G236del / S267K / L368D / K370S / N208D / Q295E / N384D / Q418E / N421D and the first Fc domain comprises the amino acid variants E233P / L234V / L235A / G236del / S267K / S364K / E357Q, where numbering is according to EU numbering. In exemplary embodiments, the first and second variant Fc domains each further comprise the amino acid variants 428L / 434S.

[0466] In some embodiments of the anti-CD28 x anti-PSMA antibody, the scFv linker is selected from GKPGSGKPGSGKPGSGKPGS (SEQ ID NO: 443), GGSEGKSSGSGSESKSTGGS (SEQ ID NO: 456), and GGGSGGSGGCPPCGGSGG (SEQ ID NO: 457).

[0467] In another aspect, provided herein is a bispecific antibody comprising a first antigen-binding domain that binds to PSMA and a second antigen-binding domain that binds to CD28.

[0468] The first antigen-binding domain (i.e., the PSMA-binding domain) comprises:

[0469] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 206; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 210; or

[0470] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 214; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 218; or

[0471] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 222; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 226; or

[0472] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 230; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 234; or

[0473] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 238; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 242; or

[0474] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 246; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 250; or

[0475] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 254; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 258; or

[0476] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 262; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 266; or

[0477] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 270; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 274; or

[0478] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 278; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 282; or

[0479] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 286; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 290; or

[0480] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 294; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 298; or

[0481] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 302; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 306; or

[0482] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 310; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 314; or

[0483] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 318; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 322; or

[0484] (i) a VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 326; and (ii) a VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 330; or

[0485] (i) VH1 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of VH vhCDR1, vhCDR2, and vhCDR3, respectively, having the amino acid sequence of SEQ ID NO: 334; and (ii) VL1 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of VL vlCDR1, vlCDR2, and vlCDR3, respectively, having the amino acid sequence of SEQ ID NO: 338. Includes.

[0486] The second antigen-binding domain (i.e., the CD28-binding domain)

[0487] i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 9; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 13; or

[0488] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 31; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 35; or

[0489] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 39; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 43; or

[0490] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 47; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 51; or

[0491] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 55; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 59; or

[0492] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 63; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 67; or

[0493] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 86; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 90; or

[0494] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 94; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 98; or

[0495] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 102; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 106; or

[0496] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 110; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 114; or

[0497] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 118; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 122; or

[0498] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 126; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 130; or

[0499] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 134; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 138; or

[0500] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 142; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 146; or

[0501] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 150; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 154; or

[0502] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 158; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 162; or

[0503] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 166; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 170; or

[0504] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 174; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 178; or

[0505] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 182; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 186; or

[0506] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 190; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 194; or

[0507] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 198; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 202; or

[0508] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 380; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 384; or

[0509] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 388; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 392; or

[0510] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 396; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 400; or

[0511] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 404; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 408; or

[0512] (i) a VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of a VH having the amino acid sequence of SEQ ID NO: 412; and (ii) a VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of a VL having the amino acid sequence of SEQ ID NO: 416; or

[0513] (i) VH2 comprising vhCDR1, vhCDR2, and vhCDR3 having the amino acid sequences of vhCDR1, vhCDR2, and vhCDR3, respectively, of VH having the amino acid sequence of SEQ ID NO: 420; and (ii) VL2 comprising vlCDR1, vlCDR2, and vlCDR3 having the amino acid sequences of vlCDR1, vlCDR2, and vlCDR3, respectively, of VL having the amino acid sequence of SEQ ID NO: 424. Includes.

[0514] In some embodiments, (i) the vhCDR1, vhCDR2, vhCDR3, vlCDR1, vlCDR2, and vlCDR3 amino acid sequences are numbered according to the Kabat numbering system; (ii) the vhCDR1, vhCDR2, vhCDR3, vlCDR1, vlCDR2, and vlCDR3 amino acid sequences are numbered according to the Chothia numbering system; (iii) the vhCDR1, vhCDR2, vhCDR3, vlCDR1, vlCDR2, and vlCDR3 amino acid sequences are numbered according to the AbM numbering system; and (iv) the vhCDR1, vhCDR2, vhCDR3, vlCDR1, vlCDR2, and vlCDR3 amino acid sequences are numbered according to the AbM numbering system. (v) the CDR2 and vlCDR3 amino acid sequences are numbered according to the Contact numbering system; (v) the vhCDR1, vhCDR2, vhCDR3, vlCDR1, vlCDR2, and vlCDR3 amino acid sequences are numbered according to the IMGT numbering system; (vi) the vhCDR1, vhCDR2, vhCDR3, vlCDR1, vlCDR2, and vlCDR3 amino acid sequences are numbered according to the Kabat+Chothia numbering system; and / or the vhCDR1, vhCDR2, vhCDR3, vlCDR1, vlCDR2, and vlCDR3 amino acid sequences are numbered according to the Xencor numbering system.

[0515] In another aspect, provided herein is a bispecific antibody comprising a first antigen-binding domain that binds to PSMA and a second antigen-binding domain that binds to CD28.

[0516] The first antigen-binding domain (i.e., the PSMA-binding domain) comprises:

[0517] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 207; a vhCDR2 having the amino acid sequence of SEQ ID NO: 208; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 209; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 211; a vlCDR2 having the amino acid sequence of SEQ ID NO: 212; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 213; or

[0518] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 215; a vhCDR2 having the amino acid sequence of SEQ ID NO: 216; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 217; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 219; a vlCDR2 having the amino acid sequence of SEQ ID NO: 220; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 221;

[0519] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 223; a vhCDR2 having the amino acid sequence of SEQ ID NO: 224; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 225; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 227; a vlCDR2 having the amino acid sequence of SEQ ID NO: 228; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 229; or

[0520] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 231; a vhCDR2 having the amino acid sequence of SEQ ID NO: 232; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 233; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 235; a vlCDR2 having the amino acid sequence of SEQ ID NO: 236; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 237; or

[0521] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 239; a vhCDR2 having the amino acid sequence of SEQ ID NO: 240; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 241; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 243; a vlCDR2 having the amino acid sequence of SEQ ID NO: 244; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 245; or

[0522] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 247; a vhCDR2 having the amino acid sequence of SEQ ID NO: 248; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 249; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 251; a vlCDR2 having the amino acid sequence of SEQ ID NO: 252; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 253; or

[0523] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 255; a vhCDR2 having the amino acid sequence of SEQ ID NO: 256; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 257; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 259; a vlCDR2 having the amino acid sequence of SEQ ID NO: 260; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 261; or

[0524] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 263; a vhCDR2 having the amino acid sequence of SEQ ID NO: 264; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 265; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 267; a vlCDR2 having the amino acid sequence of SEQ ID NO: 268; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 269; or

[0525] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 271; a vhCDR2 having the amino acid sequence of SEQ ID NO: 212; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 273; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 275; a vlCDR2 having the amino acid sequence of SEQ ID NO: 276; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 277; or

[0526] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 279; a vhCDR2 having the amino acid sequence of SEQ ID NO: 280; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 281; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 283; a vlCDR2 having the amino acid sequence of SEQ ID NO: 284; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 285; or

[0527] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 287; a vhCDR2 having the amino acid sequence of SEQ ID NO: 288; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 289; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 291; a vlCDR2 having the amino acid sequence of SEQ ID NO: 292; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 293; or

[0528] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 295; a vhCDR2 having the amino acid sequence of SEQ ID NO: 296; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 297; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 299; a vlCDR2 having the amino acid sequence of SEQ ID NO: 300; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 301; or

[0529] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 303; a vhCDR2 having the amino acid sequence of SEQ ID NO: 304; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 305; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 307; a vlCDR2 having the amino acid sequence of SEQ ID NO: 308; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 309; or

[0530] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 311; a vhCDR2 having the amino acid sequence of SEQ ID NO: 312; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 313; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 315; a vlCDR2 having the amino acid sequence of SEQ ID NO: 316; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 317; or

[0531] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 319; a vhCDR2 having the amino acid sequence of SEQ ID NO: 320; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 321; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 323; a vlCDR2 having the amino acid sequence of SEQ ID NO: 324; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 325; or

[0532] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 327; a vhCDR2 having the amino acid sequence of SEQ ID NO: 328; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 329; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 331; a vlCDR2 having the amino acid sequence of SEQ ID NO: 332; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 333; or

[0533] (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 335; a vhCDR2 having the amino acid sequence of SEQ ID NO: 336; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 337; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 339; a vlCDR2 having the amino acid sequence of SEQ ID NO: 340; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 341. Includes.

[0534] The second antigen-binding domain (i.e., the CD28-binding domain)

[0535] (i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 10; a vhCDR2 having the amino acid sequence of SEQ ID NO: 11; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 12; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 14; a vlCDR2 having the amino acid sequence of SEQ ID NO: 15; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 16; or

[0536] (i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 32; a vhCDR2 having the amino acid sequence of SEQ ID NO: 33; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 34; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 36; a vlCDR2 having the amino acid sequence of SEQ ID NO: 37; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 38; or

[0537] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 40; a vhCDR2 having the amino acid sequence of SEQ ID NO: 41; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 42; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 44; a vlCDR2 having the amino acid sequence of SEQ ID NO: 45; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 46; or

[0538] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 48; a vhCDR2 having the amino acid sequence of SEQ ID NO: 49; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 50; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 52; a vlCDR2 having the amino acid sequence of SEQ ID NO: 53; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 54; or

[0539] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 56; a vhCDR2 having the amino acid sequence of SEQ ID NO: 57; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 58; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 60; a vlCDR2 having the amino acid sequence of SEQ ID NO: 61; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 62; or

[0540] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 64; a vhCDR2 having the amino acid sequence of SEQ ID NO: 65; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 66; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 68; a vlCDR2 having the amino acid sequence of SEQ ID NO: 69; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 70; or

[0541] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 87; a vhCDR2 having the amino acid sequence of SEQ ID NO: 88; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 89; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 91; a vlCDR2 having the amino acid sequence of SEQ ID NO: 92; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 93; or

[0542] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 95; a vhCDR2 having the amino acid sequence of SEQ ID NO: 96; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 97; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 99; a vlCDR2 having the amino acid sequence of SEQ ID NO: 100; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 101; or

[0543] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 103; a vhCDR2 having the amino acid sequence of SEQ ID NO: 104; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 105; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 107; a vlCDR2 having the amino acid sequence of SEQ ID NO: 108; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 109; or

[0544] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 111; a vhCDR2 having the amino acid sequence of SEQ ID NO: 112; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 113; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 115; a vlCDR2 having the amino acid sequence of SEQ ID NO: 116; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 117; or

[0545] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 119; a vhCDR2 having the amino acid sequence of SEQ ID NO: 120; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 121; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 123; a vlCDR2 having the amino acid sequence of SEQ ID NO: 124; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 125; or

[0546] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 127; a vhCDR2 having the amino acid sequence of SEQ ID NO: 128; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 129; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 131; a vlCDR2 having the amino acid sequence of SEQ ID NO: 132; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 133; or

[0547] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 135; a vhCDR2 having the amino acid sequence of SEQ ID NO: 136; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 137; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 139; a vlCDR2 having the amino acid sequence of SEQ ID NO: 140; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 141; or

[0548] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 143; a vhCDR2 having the amino acid sequence of SEQ ID NO: 144; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 115; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 147; a vlCDR2 having the amino acid sequence of SEQ ID NO: 149; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 149; or

[0549] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 151; a vhCDR2 having the amino acid sequence of SEQ ID NO: 152; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 153; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 155; a vlCDR2 having the amino acid sequence of SEQ ID NO: 156; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 157; or

[0550] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 159; a vhCDR2 having the amino acid sequence of SEQ ID NO: 160; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 161; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 163; a vlCDR2 having the amino acid sequence of SEQ ID NO: 164; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 165; or

[0551] (i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 167; a vhCDR2 having the amino acid sequence of SEQ ID NO: 168; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 169; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 171; a vlCDR2 having the amino acid sequence of SEQ ID NO: 172; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 173; or

[0552] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 175; a vhCDR2 having the amino acid sequence of SEQ ID NO: 176; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 177; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 179; a vlCDR2 having the amino acid sequence of SEQ ID NO: 180; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 181; or

[0553] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 183; a vhCDR2 having the amino acid sequence of SEQ ID NO: 184; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 185; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 187; a vlCDR2 having the amino acid sequence of SEQ ID NO: 188; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 189; or

[0554] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 191; a vhCDR2 having the amino acid sequence of SEQ ID NO: 192; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 193; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 195; a vlCDR2 having the amino acid sequence of SEQ ID NO: 196; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 197; or

[0555] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 199; a vhCDR2 having the amino acid sequence of SEQ ID NO: 200; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 201; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 203; a vlCDR2 having the amino acid sequence of SEQ ID NO: 204; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 205; or

[0556] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 381; a vhCDR2 having the amino acid sequence of SEQ ID NO: 382; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 383; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 385; a vlCDR2 having the amino acid sequence of SEQ ID NO: 386; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 387; or

[0557] (i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 389; a vhCDR2 having the amino acid sequence of SEQ ID NO: 390; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 391; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 393; a vlCDR2 having the amino acid sequence of SEQ ID NO: 394; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 395; or

[0558] (i) a VH comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 397; a vhCDR2 having the amino acid sequence of SEQ ID NO: 398; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 399; and (ii) a VL comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 401, a vlCDR2 having the amino acid sequence of SEQ ID NO: 402, and a vlCDR3 having the amino acid sequence of SEQ ID NO: 403; or

[0559] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 405; a vhCDR2 having the amino acid sequence of SEQ ID NO: 406; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 407; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 409; a vlCDR2 having the amino acid sequence of SEQ ID NO: 410; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 411; or

[0560] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 413; a vhCDR2 having the amino acid sequence of SEQ ID NO: 414; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 415; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 417; a vlCDR2 having the amino acid sequence of SEQ ID NO: 418; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 419; or

[0561] i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 421; a vhCDR2 having the amino acid sequence of SEQ ID NO: 422; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 423; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 425; a vlCDR2 having the amino acid sequence of SEQ ID NO: 426; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 427. Includes.

[0562] In another aspect, provided herein is a bispecific antibody comprising a first antigen-binding domain that binds to PSMA and a second antigen-binding domain that binds to CD28.

[0563] The first antigen-binding domain (i.e., the PSMA-binding domain) comprises:

[0564] (i) a VH1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 206; and (ii) a VL1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 210; or

[0565] (i) a VH1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 214; and (ii) a VL1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 218; or

[0566] (i) a VH1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 222; and (ii) a VL1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 226; or

[0567] (i) a VH1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 230; and (ii) a VL1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 234; or

[0568] (i) a VH1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 238; and (ii) a VL1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 242; or

[0569] (i) a VH1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 246; and (ii) a VL1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 250; or

[0570] (i) a VH1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 254; and (ii) a VL1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 258; or

[0571] (i) a VH1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 262; and (ii) a VL1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 266; or

[0572] (i) a VH1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 270; and (ii) a VL1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 274; or

[0573] (i) a VH1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 278; and (ii) a VL1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 282; or

[0574] (i) a VH1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 286; and (ii) a VL1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 290; or

[0575] (i) a VH1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 294; and (ii) a VL1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 298; or

[0576] (i) a VH1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 302; and (ii) a VL1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 306; or

[0577] (i) a VH1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 310; and (ii) a VL1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 314; or

[0578] (i) a VH1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 318; and (ii) a VL1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 322; or

[0579] (i) a VH1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 326; and (ii) a VL1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 330; or

[0580] (i) a VH1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 334; and (ii) a VL1 having an amino acid sequence at least about 95% identical to SEQ ID NO: 338. Includes.

[0581] The second antigen-binding domain (i.e., the CD28-binding domain)

[0582] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO:9; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO:13; or

[0583] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 31; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 35; or

[0584] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 39; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 43; or

[0585] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 47; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 51; or

[0586] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 55; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 59; or

[0587] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 63; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 67; or

[0588] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 86; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 90; or

[0589] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 94; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 98; or

[0590] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 102; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 106; or

[0591] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 110; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 114; or

[0592] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 118; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 122; or

[0593] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 126; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 130; or

[0594] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 134; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 138; or

[0595] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 142; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 146; or

[0596] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 150; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 154; or

[0597] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 158; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 162; or

[0598] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 166; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 170; or

[0599] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 174; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 178; or

[0600] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 182; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 186; or

[0601] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 190; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 194; or

[0602] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 198; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 202; or

[0603] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 380; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 384; or

[0604] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 388; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 392; or

[0605] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 396; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 400; or

[0606] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 404; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 408; or

[0607] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 412; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 416; or

[0608] (i) a VH2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 420; and (ii) a VL2 having an amino acid sequence at least about 95% identical to SEQ ID NO: 424. Includes.

[0609] In some embodiments of the bispecific antibody, the antibody is a humanized antibody. In certain embodiments, the antibody is a human antibody.

[0610] In some embodiments of the bispecific antibody, the antibody is an IgG antibody. In some embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody. In an exemplary embodiment, the IgG antibody is an IgG1 antibody.

[0611] In some embodiments of the bispecific antibody, the first antigen-binding domain binds the PSMA antigen. In exemplary embodiments, the first antigen-binding domain binds a PSMA epitope. In some embodiments, the first antigen-binding domain specifically binds to PSMA.

[0612] In some embodiments of the bispecific antibody, vhCDR1, vhCDR2, vhCDR3, vlCDR1, vlCDR2, and vlCDR3 of the first antigen-binding domain form a binding site for an antigen of PSMA. In certain embodiments, vhCDR1, vhCDR2, vhCDR3, vlCDR1, vlCDR2, and vlCDR3 of the first antigen-binding domain form a binding site for an epitope of PSMA.

[0613] In some embodiments of the bispecific antibody, the second antigen-binding domain binds the CD28 antigen. In exemplary embodiments, the second antigen-binding domain binds a CD28 epitope. In some embodiments, the second antigen-binding domain specifically binds CD28.

[0614] In some embodiments of the bispecific antibody, vhCDR1, vhCDR2, vhCDR3, vlCDR1, vlCDR2 and vlCDR3 of the second antigen-binding domain form a binding site for an antigen on CD28. In an exemplary embodiment, vhCDR1, vhCDR2, vhCDR3, vlCDR1, vlCDR2 and vlCDR3 of the second antigen-binding domain form a binding site for an epitope on CD28.

[0615] In some embodiments of the bispecific antibody, PSMA is present on the surface of a cell. In certain embodiments, the cell is a prostate cell. In an exemplary embodiment, the cell is a prostate cancer cell.

[0616] In some embodiments of the bispecific antibody, the antibody comprises a first Fc domain and a second Fc domain. In exemplary embodiments, the first Fc domain and the second Fc domain are each variant Fc domains.

[0617] In some embodiments, one of the first and second Fc domains is the heterodimerization variant T366W and the other of the first and second Fc domains comprises the heterodimerization variant T366S / L368A / Y407V, where the numbering is according to EU numbering. In exemplary embodiments, the first Fc domain comprises the heterodimerization variant T366W and the second Fc domain comprises the heterodimerization variant T366S / L368A / Y407V.

[0618] In some embodiments, the first and second Fc domains each comprise one or more reduced variants. In exemplary embodiments, the one or more reduced variants comprise L234A / L235A / D265S, where the numbering is according to EU numbering.

[0619] In some embodiments, the first or second Fc domain comprises the purified variant H435R / Y436F, where the numbering is according to EU numbering. In an exemplary embodiment, the second Fc domain comprises the purified variant H435R / Y436F.

[0620] In certain embodiments, the first Fc domain comprises amino acid substitutions L234A / L235A / D265S / LT366W and the second Fc domain comprises amino acid substitutions L234A / L235A / D265S / T366S / L368A / Y407V / H435R / Y436F, where numbering is according to EU numbering. In exemplary embodiments, the first and second Fc domains each further comprise amino acid substitutions M252Y / S254T / T256E, where numbering is according to EU numbering.

[0621] In some embodiments, the first and second Fc domains comprise a set of heterodimerization variants selected from the following heterodimerization variants: S364K / E357Q:L368D / K370S; S364K:L368D / K370S; S364K:L368E / K370S; D401K:T411E / K360E / Q362E; and T366W:T366S / L368A / Y407V, where numbering is according to EU numbering. In exemplary embodiments, the first and second Fc domains comprise the heterodimerization variant S364K / E357Q:L368D / K370S, where numbering is according to EU numbering.

[0622] In some embodiments, the first and second Fc domains each comprise one or more reduced variants, hi some embodiments, the one or more reduced variants comprise E233P / L234V / L235A / G236del / S267K, where the numbering is according to EU numbering.

[0623] In some embodiments of the bispecific antibody, the bispecific antibody is in a 1+1 Fab-scFv-Fc format. These antibodies comprise a) a first monomer; b) a second monomer; and c) a light chain. The first monomer comprises i) a single-chain variable fragment (scFv); and ii) a first Fc domain, where the scFv is covalently linked to the N-terminus of the first Fc domain using a domain linker. The second monomer comprises, from N-terminus to C-terminus, VH1-CH1-hinge-CH2-CH3, where VH1 is the first variable heavy domain and CH2-CH3 are the second Fc domain. The light chain comprises, from N-terminus to C-terminus, VL1-CL, where VL1 is the first variable light domain and CL is the constant light domain. The scFv comprises a second VH domain (VH2), an scFv linker, and a second variable light domain (VL2). VH1 and VL1 together form the first antigen binding domain (ABD), and VH2 and VL2 together form the second ABD.

[0624] In some embodiments, one of the first or second monomer further comprises a pI variant, in some embodiments, the CH1-hinge-CH2-CH3 of the second monomer comprises the pI variants N208D / Q295E / N384D / Q418E / N421D, where the numbering is according to EU numbering.

[0625] In exemplary embodiments, the CH1-hinge-CH2-CH3 of the second monomer comprises the amino acid variants E233P / L234V / L235A / G236del / S267K / L368D / K370S / N208D / Q295E / N384D / Q418E / N421D and the first Fc domain comprises the amino acid variants E233P / L234V / L235A / G236del / S267K / S364K / E357Q, where numbering is according to EU numbering. In exemplary embodiments, the first and second variant Fc domains each further comprise the amino acid variants 428L / 434S.

[0626] In an exemplary embodiment of a bispecific 1+1 Fab-scFv-Fc format antibody, the scFv linker is selected from GKPGSGKPGSGKPGSGKPGS (SEQ ID NO: 443), GGSEGKSSGSGSESKSTGGS (SEQ ID NO: 456), and GGGSGGSGGCPPCGGSGG (SEQ ID NO: 457).

[0627] In another aspect, provided herein is a heterodimeric antibody comprising: a) a first monomer having the amino acid sequence of SEQ ID NO: 351; b) a second monomer having the amino acid sequence of SEQ ID NO: 352; and c) a light chain having the amino acid sequence of SEQ ID NO: 353.

[0628] In yet another aspect, provided herein is a heterodimeric antibody comprising: a) a first monomer having the amino acid sequence of SEQ ID NO: 342; b) a second monomer having the amino acid sequence of SEQ ID NO: 343; and c) a light chain having the amino acid sequence of SEQ ID NO: 344.

[0629] In one aspect, provided herein is a bispecific antibody comprising: a) a first antigen-binding domain having (i) a VH1 having the amino acid sequence of SEQ ID NO: 214; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 218; and b) a second antigen-binding domain having (i) a VH2 having the amino acid sequence of SEQ ID NO: 39; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 43.

[0630] In one aspect, provided herein is a bispecific antibody comprising: a) a first antigen-binding domain having: (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 215; a vhCDR2 having the amino acid sequence of SEQ ID NO: 216; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 217; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 219; a vlCDR2 having the amino acid sequence of SEQ ID NO: 220; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 221; and b) a second antigen-binding domain having: (i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 40; a vhCDR2 having the amino acid sequence of SEQ ID NO: 41; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 42; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 44; a vlCDR2 having the amino acid sequence of SEQ ID NO: 45; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 46.

[0631] In another aspect, provided herein is a bispecific antibody comprising: a) a first antigen-binding domain having (i) a VH1 having the amino acid sequence of SEQ ID NO: 214; and (ii) a VL1 having the amino acid sequence of SEQ ID NO: 218; and b) a second antigen-binding domain having (i) a VH2 having the amino acid sequence of SEQ ID NO: 396; and (ii) a VL2 having the amino acid sequence of SEQ ID NO: 400.

[0632] In one aspect, provided herein is a bispecific antibody comprising: a) a first antigen-binding domain having: (i) a VH1 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 215; a vhCDR2 having the amino acid sequence of SEQ ID NO: 216; and a vhCDR3 having the amino acid sequence of SEQ ID NO: 217; and (ii) a VL1 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 219; a vlCDR2 having the amino acid sequence of SEQ ID NO: 220; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 221; and b) a second antigen-binding domain having: (i) a VH2 comprising a vhCDR1 having the amino acid sequence of SEQ ID NO: 397; a vhCDR2 having the amino acid sequence of SEQ ID NO: 398; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 399; and (ii) a VL2 comprising a vlCDR1 having the amino acid sequence of SEQ ID NO: 401; a vlCDR2 having the amino acid sequence of SEQ ID NO: 402; and a vlCDR3 having the amino acid sequence of SEQ ID NO: 403.

[0633] Also provided herein are nucleic acid compositions comprising nucleic acids encoding the antibodies described herein, expression vector compositions comprising such nucleic acids, host cells for producing the antibodies comprising the expression vector compositions, and methods of producing the antibodies.

[0634] In another aspect, provided herein is a method of treating prostate cancer in a patient in need thereof, the method comprising administering to the patient an anti-CD28 x anti-PSMA antibody described herein.

[0635] In yet another aspect, provided herein is a method of treating prostate cancer in a patient in need thereof, comprising administering to the patient: a) an anti-CD28 x anti-PSMA; and b) an anti-CD3 x anti-PSMA anti-CD3 x anti-B7H3, anti-CD3 x anti-hK2, or anti-CD3 x anti-TMEFF2 antibody described herein.

[0636] In one aspect, provided herein is a method of enhancing T cell proliferation in the presence of PSMA-expressing cells, comprising contacting the cells with anti-CD28 x anti-PSMA as described herein. In some embodiments, the PSMA-expressing cells are prostate cells.

[0637] In another aspect, provided herein is a method of inhibiting the growth or proliferation of PSMA-expressing cells, comprising contacting the cells with an anti-CD28 x anti-PSMA antibody described herein. In some embodiments, the PSMA-expressing cells are prostate cells. [Brief explanation of the drawings]

[0638] [Figure 1A] The sequences of human, mouse, and cynomolgus monkey CD28 are shown. Such CD28s are useful for the development of cross-reactive CD28 antigen-binding domains to facilitate clinical development. [Figure 1B] The sequences of human, mouse, and cynomolgus monkey CD28 are shown. Such CD28s are useful for the development of cross-reactive CD28 antigen-binding domains to facilitate clinical development. [Figure 2A] The sequences of human, mouse, and cynomolgus PSMA are shown, which are useful for the development of cross-reactive PSMA antigen-binding domains to facilitate clinical development. [Figure 2B] The sequences of human, mouse, and cynomolgus PSMA are shown, which are useful for the development of cross-reactive PSMA antigen-binding domains to facilitate clinical development. [Figure 3A]Useful pairs of heterodimerization variant sets (including skew and pI variants) are shown. In Figure 3F, variants are present for which no corresponding "monomer 2" variant exists. Such variants can be used alone on either monomer of a bispecific antibody (e.g., a PSMAxCD28 bsAb), or the pI variant can be included on the non-scFv side of a format that utilizes, for example, an scFv as a component and an appropriate charged scFv linker. The pI variant can be used on the second monomer that utilizes an scFv as the CD28-binding domain. Suitable charged linkers are shown in Figures 6A-6B. [Figure 3B] Useful pairs of heterodimerization variant sets (including skew and pI variants) are shown. In Figure 3F, variants are present for which there is no corresponding "monomer 2" variant. Such variants can be used alone in either monomer of a bispecific antibody (e.g., a PSMAxCD28 bsAb) or, for example, as pI variants, can be included on the non-scFv side of a format utilizing an scFv as a component; an appropriately charged scFv linker can be used in the second monomer utilizing an scFv as the CD28-binding domain. Suitable charged linkers are shown in Figures 6A-6B. [Figure 3C] Useful pairs of heterodimerization variant sets (including skew and pI variants) are shown. In Figure 3F, variants are present for which there is no corresponding "monomer 2" variant. Such variants can be used alone in either monomer of a bispecific antibody (e.g., a PSMAxCD28 bsAb) or, for example, as pI variants, can be included on the non-scFv side of a format utilizing an scFv as a component; an appropriately charged scFv linker can be used in the second monomer utilizing an scFv as the CD28-binding domain. Suitable charged linkers are shown in Figures 6A-6B. [Figure 3D]Useful pairs of heterodimerization variant sets (including skew and pI variants) are shown. In Figure 3F, variants are present for which there is no corresponding "monomer 2" variant. Such variants can be used alone in either monomer of a bispecific antibody (e.g., a PSMAxCD28 bsAb) or, for example, as pI variants, can be included on the non-scFv side of a format utilizing an scFv as a component; an appropriately charged scFv linker can be used in the second monomer utilizing an scFv as the CD28-binding domain. Suitable charged linkers are shown in Figures 6A-6B. [Figure 3E] Useful pairs of heterodimerization variant sets (including skew and pI variants) are shown. In Figure 3F, variants are present for which there is no corresponding "monomer 2" variant. Such variants can be used alone in either monomer of a bispecific antibody (e.g., a PSMAxCD28 bsAb) or, for example, as pI variants, can be included on the non-scFv side of a format utilizing an scFv as a component; an appropriately charged scFv linker can be used in the second monomer utilizing an scFv as the CD28-binding domain. Suitable charged linkers are shown in Figures 6A-6B. [Figure 3F] Useful pairs of heterodimerization variant sets (including skew and pI variants) are shown. In Figure 3F, variants are present for which there is no corresponding "monomer 2" variant. Such variants can be used alone in either monomer of a bispecific antibody (e.g., a PSMAxCD28 bsAb) or, for example, as pI variants, can be included on the non-scFv side of a format utilizing an scFv as a component; an appropriately charged scFv linker can be used in the second monomer utilizing an scFv as the CD28-binding domain. Suitable charged linkers are shown in Figures 6A-6B. [Figure 4]A list of isosteric variant antibody constant regions and their respective substitutions is shown. pI_(-) indicates a lower pI variant, while pI_(+) indicates a higher pI variant. These variants can optionally and independently be combined with other variants, including heterodimerization variants, as outlined herein. [Figure 5] Useful reduced variants (also referred to as "knockout" or "KO" variants) that reduce FcγR binding are shown. In some embodiments, such reduced variants are contained in the Fc domains of both monomers of the subject antibodies described herein. In other embodiments, the reduced variant is contained in only one variant Fc domain. [Figure 6A] As described herein, numerous charged scFv linkers are shown for use in increasing or decreasing the pI of a subject heterodimeric bispecific antibody (e.g., PSMA x CD28 bsAb) that utilizes one or more scFv components. (+H) Positive linkers are particularly utilized herein, particularly with the anti-CD28 VL and VH sequences shown herein. A single prior art scFv linker bearing a single charge is referred to as "Whitlow" after Whitlow et al., Protein Engineering 6(8):989-995 (1993). It should be noted that this linker was used in scFvs to reduce aggregation and improve proteolytic stability. Such charged scFv linkers can be used in any of the subject antibody formats disclosed herein that include scFvs (e.g., 1+1 Fab-scFv-Fc and 2+1 Fab2-scFv-Fc formats). [Figure 6B]As described herein, numerous charged scFv linkers are shown for use in increasing or decreasing the pI of a subject heterodimeric bispecific antibody (e.g., PSMA x CD28 bsAb) that utilizes one or more scFv components. (+H) Positive linkers are particularly utilized herein, particularly with the anti-CD28 VL and VH sequences shown herein. A single prior art scFv linker bearing a single charge is referred to as "Whitlow" after Whitlow et al., Protein Engineering 6(8):989-995 (1993). It should be noted that this linker was used in scFvs to reduce aggregation and improve proteolytic stability. Such charged scFv linkers can be used in any of the subject antibody formats disclosed herein that include scFvs (e.g., 1+1 Fab-scFv-Fc and 2+1 Fab2-scFv-Fc formats). [Figure 7] A number of exemplary domain linkers are shown. In some embodiments, these linkers are utilized to link a single-chain Fv to an Fc chain. In some embodiments, these linkers can be combined in any orientation. For example, a GGGGS (SEQ ID NO: 458) linker can be combined with a "lower half-hinge" linker at the N-terminus or C-terminus. [Figure 8] We present a particularly useful bispecific antibody platform for the PSMAxCD28 bsAb of the present invention. Although the platform is described herein in the context of a 1+1 Fab-scFv-Fc format, it can be adapted for use in other bispecific antibody formats. [Figure 9] 1A-1D show various heterodimeric variant amino acid substitutions that may be used in the heterodimeric antibodies described herein. [Figure 10A]

[0039] Figure 1 shows the sequences of several useful heterodimeric PSMAxCD28 bsAb scaffolds based on human IgGl, without cytokine sequences. Heterodimeric Fc scaffold 1 is based on human IgGl (356E / 358M allotype) and contains the L368D / K370S scuba variant and Q295E / N384D / Q418E / N421D pI variants on the first heterodimeric Fc chain, the S364K / E357Q scuba variant on the second heterodimeric Fc chain, and the E233P / L234V / L235A / G236del / S267K reduced variants on both chains. Heterodimeric Fc scaffold 2 is based on human IgG1 (356E / 358M allotype) and comprises the L368D / K370S scuba variant and the Q295E / N384D / Q418E / N421D pI variants on the first heterodimeric Fc chain, the S364K scuba variant on the second heterodimeric Fc chain, and the E233P / L234V / L235A / G236del / S267K reduced variants on both chains. Heterodimeric Fc scaffold 3 is based on human IgG1 (356E / 358M allotype) and contains the L368E / K370S scuba variant and Q295E / N384D / Q418E / N421D pI variants on the first heterodimeric Fc chain, the S364K scuba variant on the second heterodimeric Fc chain, and the E233P / L234V / L235A / G236del / S267K reduced variants on both chains. Heterodimeric Fc scaffold 4 is based on human IgG1 (356E / 358M allotype) and contains K360E / Q362E / T411E scubariant and Q295E / N384D / Q418E / N421D pI variants on the first heterodimeric Fc chain, a D401K scubariant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants on both chains.Heterodimeric Fc scaffold 5 is based on human IgG1 (356D / 358L allotype) and comprises the L368D / K370S scuba variant and the Q295E / N384D / Q418E / N421D pI variants on the first heterodimeric Fc chain, the S364K / E357Q scuba variant on the second heterodimeric Fc chain, and the E233P / L234V / L235A / G236del / S267K reduced variants on both chains. Heterodimeric Fc scaffold 6 is based on human IgG1 (356E / 358M allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an N297A variant that eliminates glycosylation on both chains. Heterodimeric Fc scaffold 7 is based on human IgG1 (356E / 358M allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an N297S variant that eliminates glycosylation on both chains. Heterodimeric Fc scaffold 8 is based on human IgG4 and comprises the L368D / K370S scuba variant and the Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, the S364K / E357Q scuba variant on the second heterodimeric Fc chain, and the S228P (S241P according to EU numbering, Kabat) variant, which reduces Fab arm exchange (as known in the art), on both chains. Heterodimeric Fc scaffold 9 is based on human IgG2 and comprises the L368D / K370S scuba variant and the Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, and the S364K / E357Q scuba variant on the second heterodimeric Fc chain.The heterodimeric Fc scaffold 10 is based on human IgG2 and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and an S267K reduced variant on both chains. Heterodimeric Fc scaffold 11 is based on human IgG1 (356E / 358M allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an M428L / N434S extended variant on both chains. Heterodimeric Fc scaffold 12 is based on human IgG1 (356E / 358M allotype) and comprises an L368D / K370S variant on the first heterodimeric Fc chain, an S364K / E357Q variant and a P217R / P229R / N276K pI variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants on both chains. Heterodimeric Fc scaffold 13 is based on human IgG1 (356E / 358M allotype) and comprises a T366W variant on the first heterodimeric Fc chain, a T366S / L368A / Y407V variant and a H435R / Y436F refined variant on the second heterodimeric Fc chain, and L234A / L235A / D265S reduced variants on both chains. Heterodimeric Fc scaffold 14 is based on human IgG1 (356E / 358M allotype) and comprises a T366W scuba variant on the first heterodimeric Fc chain, a T366S / L368A / Y407V scuba variant and a H435R / Y436F purified variant on the second heterodimeric Fc chain, and L234A / L235A / D265S reduced variants and M252Y / S254T / T256E half-life extended variants on both chains.Heterodimeric Fc scaffold 15 is based on human IgG1 (356D / 358L allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an M428L / N434S extended variant on both chains. Heterodimeric Fc scaffold 16 is based on human IgG1 (356E / 358M allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an M428L / N434A extended variant on both chains. Heterodimeric Fc scaffold 17 is based on human IgG1 (356D / 358L allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an M428L / N434A Xtend variant on both chains. Included in each of these scaffolds are sequences that are 90, 95, 98, and 99% identical (as defined herein) to the depicted sequences and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more additional amino acid substitutions (when compared to the parent human IgG1 (or IgG2 or IgG4, depending on the scaffold), as will be understood by one of skill in the art, as compared to the "parent" in the diagram, which already contains multiple amino acid modifications). That is, the depicted scaffolds can contain additional amino acid modifications (usually amino acid substitutions) in addition to or as an alternative to the skew, pI, and reduced variants contained within the scaffolds in this diagram. The scaffolds shown herein can also include deletions of the C-terminal glycine (K446_) and / or lysine (K447_).C-terminal glycine and / or lysine deletions can be intentionally engineered to reduce heterogeneity or in the context of a given bispecific format, such as a mAb-scFv format, and can also occur naturally, for example, during production and storage. [Figure 10B]

[0039] Figure 1 shows the sequences of several useful heterodimeric PSMAxCD28 bsAb scaffolds based on human IgGl, without cytokine sequences. Heterodimeric Fc scaffold 1 is based on human IgGl (356E / 358M allotype) and contains the L368D / K370S scuba variant and Q295E / N384D / Q418E / N421D pI variants on the first heterodimeric Fc chain, the S364K / E357Q scuba variant on the second heterodimeric Fc chain, and the E233P / L234V / L235A / G236del / S267K reduced variants on both chains. Heterodimeric Fc scaffold 2 is based on human IgG1 (356E / 358M allotype) and comprises the L368D / K370S scuba variant and the Q295E / N384D / Q418E / N421D pI variants on the first heterodimeric Fc chain, the S364K scuba variant on the second heterodimeric Fc chain, and the E233P / L234V / L235A / G236del / S267K reduced variants on both chains. Heterodimeric Fc scaffold 3 is based on human IgG1 (356E / 358M allotype) and contains the L368E / K370S scuba variant and Q295E / N384D / Q418E / N421D pI variants on the first heterodimeric Fc chain, the S364K scuba variant on the second heterodimeric Fc chain, and the E233P / L234V / L235A / G236del / S267K reduced variants on both chains. Heterodimeric Fc scaffold 4 is based on human IgG1 (356E / 358M allotype) and contains K360E / Q362E / T411E scubariant and Q295E / N384D / Q418E / N421D pI variants on the first heterodimeric Fc chain, a D401K scubariant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants on both chains.Heterodimeric Fc scaffold 5 is based on human IgG1 (356D / 358L allotype) and comprises the L368D / K370S scuba variant and the Q295E / N384D / Q418E / N421D pI variants on the first heterodimeric Fc chain, the S364K / E357Q scuba variant on the second heterodimeric Fc chain, and the E233P / L234V / L235A / G236del / S267K reduced variants on both chains. Heterodimeric Fc scaffold 6 is based on human IgG1 (356E / 358M allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an N297A variant that eliminates glycosylation on both chains. Heterodimeric Fc scaffold 7 is based on human IgG1 (356E / 358M allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an N297S variant that eliminates glycosylation on both chains. Heterodimeric Fc scaffold 8 is based on human IgG4 and comprises the L368D / K370S scuba variant and the Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, the S364K / E357Q scuba variant on the second heterodimeric Fc chain, and the S228P (S241P according to EU numbering, Kabat) variant, which reduces Fab arm exchange (as known in the art), on both chains. Heterodimeric Fc scaffold 9 is based on human IgG2 and comprises the L368D / K370S scuba variant and the Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, and the S364K / E357Q scuba variant on the second heterodimeric Fc chain.The heterodimeric Fc scaffold 10 is based on human IgG2 and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and an S267K reduced variant on both chains. Heterodimeric Fc scaffold 11 is based on human IgG1 (356E / 358M allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an M428L / N434S extended variant on both chains. Heterodimeric Fc scaffold 12 is based on human IgG1 (356E / 358M allotype) and comprises an L368D / K370S variant on the first heterodimeric Fc chain, an S364K / E357Q variant and a P217R / P229R / N276K pI variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants on both chains. Heterodimeric Fc scaffold 13 is based on human IgG1 (356E / 358M allotype) and comprises a T366W variant on the first heterodimeric Fc chain, a T366S / L368A / Y407V variant and a H435R / Y436F refined variant on the second heterodimeric Fc chain, and L234A / L235A / D265S reduced variants on both chains. Heterodimeric Fc scaffold 14 is based on human IgG1 (356E / 358M allotype) and comprises a T366W scuba variant on the first heterodimeric Fc chain, a T366S / L368A / Y407V scuba variant and a H435R / Y436F purified variant on the second heterodimeric Fc chain, and L234A / L235A / D265S reduced variants and M252Y / S254T / T256E half-life extended variants on both chains.Heterodimeric Fc scaffold 15 is based on human IgG1 (356D / 358L allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an M428L / N434S extended variant on both chains. Heterodimeric Fc scaffold 16 is based on human IgG1 (356E / 358M allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an M428L / N434A extended variant on both chains. Heterodimeric Fc scaffold 17 is based on human IgG1 (356D / 358L allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an M428L / N434A Xtend variant on both chains. Included in each of these scaffolds are sequences that are 90, 95, 98, and 99% identical (as defined herein) to the depicted sequences and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more additional amino acid substitutions (when compared to the parent human IgG1 (or IgG2 or IgG4, depending on the scaffold), as will be understood by one of skill in the art, as compared to the "parent" in the diagram, which already contains multiple amino acid modifications). That is, the depicted scaffolds can contain additional amino acid modifications (usually amino acid substitutions) in addition to or as an alternative to the skew, pI, and reduced variants contained within the scaffolds in this diagram. The scaffolds shown herein can also include deletions of the C-terminal glycine (K446_) and / or lysine (K447_).C-terminal glycine and / or lysine deletions can be intentionally engineered to reduce heterogeneity or in the context of a given bispecific format, such as a mAb-scFv format, and can also occur naturally, for example, during production and storage. [Figure 10C]

[0039] Figure 1 shows the sequences of several useful heterodimeric PSMAxCD28 bsAb scaffolds based on human IgGl, without cytokine sequences. Heterodimeric Fc scaffold 1 is based on human IgGl (356E / 358M allotype) and contains the L368D / K370S scuba variant and Q295E / N384D / Q418E / N421D pI variants on the first heterodimeric Fc chain, the S364K / E357Q scuba variant on the second heterodimeric Fc chain, and the E233P / L234V / L235A / G236del / S267K reduced variants on both chains. Heterodimeric Fc scaffold 2 is based on human IgG1 (356E / 358M allotype) and comprises the L368D / K370S scuba variant and the Q295E / N384D / Q418E / N421D pI variants on the first heterodimeric Fc chain, the S364K scuba variant on the second heterodimeric Fc chain, and the E233P / L234V / L235A / G236del / S267K reduced variants on both chains. Heterodimeric Fc scaffold 3 is based on human IgG1 (356E / 358M allotype) and contains the L368E / K370S scuba variant and Q295E / N384D / Q418E / N421D pI variants on the first heterodimeric Fc chain, the S364K scuba variant on the second heterodimeric Fc chain, and the E233P / L234V / L235A / G236del / S267K reduced variants on both chains. Heterodimeric Fc scaffold 4 is based on human IgG1 (356E / 358M allotype) and contains K360E / Q362E / T411E scubariant and Q295E / N384D / Q418E / N421D pI variants on the first heterodimeric Fc chain, a D401K scubariant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants on both chains.Heterodimeric Fc scaffold 5 is based on human IgG1 (356D / 358L allotype) and comprises the L368D / K370S scuba variant and the Q295E / N384D / Q418E / N421D pI variants on the first heterodimeric Fc chain, the S364K / E357Q scuba variant on the second heterodimeric Fc chain, and the E233P / L234V / L235A / G236del / S267K reduced variants on both chains. Heterodimeric Fc scaffold 6 is based on human IgG1 (356E / 358M allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an N297A variant that eliminates glycosylation on both chains. Heterodimeric Fc scaffold 7 is based on human IgG1 (356E / 358M allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an N297S variant that eliminates glycosylation on both chains. Heterodimeric Fc scaffold 8 is based on human IgG4 and comprises the L368D / K370S scuba variant and the Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, the S364K / E357Q scuba variant on the second heterodimeric Fc chain, and the S228P (S241P according to EU numbering, Kabat) variant, which reduces Fab arm exchange (as known in the art), on both chains. Heterodimeric Fc scaffold 9 is based on human IgG2 and comprises the L368D / K370S scuba variant and the Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, and the S364K / E357Q scuba variant on the second heterodimeric Fc chain.The heterodimeric Fc scaffold 10 is based on human IgG2 and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and an S267K reduced variant on both chains. Heterodimeric Fc scaffold 11 is based on human IgG1 (356E / 358M allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an M428L / N434S extended variant on both chains. Heterodimeric Fc scaffold 12 is based on human IgG1 (356E / 358M allotype) and comprises an L368D / K370S variant on the first heterodimeric Fc chain, an S364K / E357Q variant and a P217R / P229R / N276K pI variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants on both chains. Heterodimeric Fc scaffold 13 is based on human IgG1 (356E / 358M allotype) and comprises a T366W variant on the first heterodimeric Fc chain, a T366S / L368A / Y407V variant and a H435R / Y436F refined variant on the second heterodimeric Fc chain, and L234A / L235A / D265S reduced variants on both chains. Heterodimeric Fc scaffold 14 is based on human IgG1 (356E / 358M allotype) and comprises a T366W scuba variant on the first heterodimeric Fc chain, a T366S / L368A / Y407V scuba variant and a H435R / Y436F purified variant on the second heterodimeric Fc chain, and L234A / L235A / D265S reduced variants and M252Y / S254T / T256E half-life extended variants on both chains.Heterodimeric Fc scaffold 15 is based on human IgG1 (356D / 358L allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an M428L / N434S extended variant on both chains. Heterodimeric Fc scaffold 16 is based on human IgG1 (356E / 358M allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an M428L / N434A extended variant on both chains. Heterodimeric Fc scaffold 17 is based on human IgG1 (356D / 358L allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an M428L / N434A Xtend variant on both chains. Included in each of these scaffolds are sequences that are 90, 95, 98, and 99% identical (as defined herein) to the depicted sequences and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more additional amino acid substitutions (when compared to the parent human IgG1 (or IgG2 or IgG4, depending on the scaffold), as will be understood by one of skill in the art, as compared to the "parent" in the diagram, which already contains multiple amino acid modifications). That is, the depicted scaffolds can contain additional amino acid modifications (usually amino acid substitutions) in addition to or as an alternative to the skew, pI, and reduced variants contained within the scaffolds in this diagram. The scaffolds shown herein can also include deletions of the C-terminal glycine (K446_) and / or lysine (K447_).C-terminal glycine and / or lysine deletions can be intentionally engineered to reduce heterogeneity or in the context of a given bispecific format, such as a mAb-scFv format, and can also occur naturally, for example, during production and storage. [Figure 10D]

[0039] Figure 1 shows the sequences of several useful heterodimeric PSMAxCD28 bsAb scaffolds based on human IgGl, without cytokine sequences. Heterodimeric Fc scaffold 1 is based on human IgGl (356E / 358M allotype) and contains the L368D / K370S scuba variant and Q295E / N384D / Q418E / N421D pI variants on the first heterodimeric Fc chain, the S364K / E357Q scuba variant on the second heterodimeric Fc chain, and the E233P / L234V / L235A / G236del / S267K reduced variants on both chains. Heterodimeric Fc scaffold 2 is based on human IgG1 (356E / 358M allotype) and comprises the L368D / K370S scuba variant and the Q295E / N384D / Q418E / N421D pI variants on the first heterodimeric Fc chain, the S364K scuba variant on the second heterodimeric Fc chain, and the E233P / L234V / L235A / G236del / S267K reduced variants on both chains. Heterodimeric Fc scaffold 3 is based on human IgG1 (356E / 358M allotype) and contains the L368E / K370S scuba variant and Q295E / N384D / Q418E / N421D pI variants on the first heterodimeric Fc chain, the S364K scuba variant on the second heterodimeric Fc chain, and the E233P / L234V / L235A / G236del / S267K reduced variants on both chains. Heterodimeric Fc scaffold 4 is based on human IgG1 (356E / 358M allotype) and contains K360E / Q362E / T411E scubariant and Q295E / N384D / Q418E / N421D pI variants on the first heterodimeric Fc chain, a D401K scubariant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants on both chains.Heterodimeric Fc scaffold 5 is based on human IgG1 (356D / 358L allotype) and comprises the L368D / K370S scuba variant and the Q295E / N384D / Q418E / N421D pI variants on the first heterodimeric Fc chain, the S364K / E357Q scuba variant on the second heterodimeric Fc chain, and the E233P / L234V / L235A / G236del / S267K reduced variants on both chains. Heterodimeric Fc scaffold 6 is based on human IgG1 (356E / 358M allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an N297A variant that eliminates glycosylation on both chains. Heterodimeric Fc scaffold 7 is based on human IgG1 (356E / 358M allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an N297S variant that eliminates glycosylation on both chains. Heterodimeric Fc scaffold 8 is based on human IgG4 and comprises the L368D / K370S scuba variant and the Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, the S364K / E357Q scuba variant on the second heterodimeric Fc chain, and the S228P (S241P according to EU numbering, Kabat) variant, which reduces Fab arm exchange (as known in the art), on both chains. Heterodimeric Fc scaffold 9 is based on human IgG2 and comprises the L368D / K370S scuba variant and the Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, and the S364K / E357Q scuba variant on the second heterodimeric Fc chain.The heterodimeric Fc scaffold 10 is based on human IgG2 and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and an S267K reduced variant on both chains. Heterodimeric Fc scaffold 11 is based on human IgG1 (356E / 358M allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an M428L / N434S extended variant on both chains. Heterodimeric Fc scaffold 12 is based on human IgG1 (356E / 358M allotype) and comprises an L368D / K370S variant on the first heterodimeric Fc chain, an S364K / E357Q variant and a P217R / P229R / N276K pI variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants on both chains. Heterodimeric Fc scaffold 13 is based on human IgG1 (356E / 358M allotype) and comprises a T366W variant on the first heterodimeric Fc chain, a T366S / L368A / Y407V variant and a H435R / Y436F refined variant on the second heterodimeric Fc chain, and L234A / L235A / D265S reduced variants on both chains. Heterodimeric Fc scaffold 14 is based on human IgG1 (356E / 358M allotype) and comprises a T366W scuba variant on the first heterodimeric Fc chain, a T366S / L368A / Y407V scuba variant and a H435R / Y436F purified variant on the second heterodimeric Fc chain, and L234A / L235A / D265S reduced variants and M252Y / S254T / T256E half-life extended variants on both chains.Heterodimeric Fc scaffold 15 is based on human IgG1 (356D / 358L allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an M428L / N434S extended variant on both chains. Heterodimeric Fc scaffold 16 is based on human IgG1 (356E / 358M allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an M428L / N434A extended variant on both chains. Heterodimeric Fc scaffold 17 is based on human IgG1 (356D / 358L allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an M428L / N434A Xtend variant on both chains. Included in each of these scaffolds are sequences that are 90, 95, 98, and 99% identical (as defined herein) to the depicted sequences and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more additional amino acid substitutions (when compared to the parent human IgG1 (or IgG2 or IgG4, depending on the scaffold), as will be understood by one of skill in the art, as compared to the "parent" in the diagram, which already contains multiple amino acid modifications). That is, the depicted scaffolds can contain additional amino acid modifications (usually amino acid substitutions) in addition to or as an alternative to the skew, pI, and reduced variants contained within the scaffolds in this diagram. The scaffolds shown herein can also include deletions of the C-terminal glycine (K446_) and / or lysine (K447_).C-terminal glycine and / or lysine deletions can be intentionally engineered to reduce heterogeneity or in the context of a given bispecific format, such as a mAb-scFv format, and can also occur naturally, for example, during production and storage. [Figure 10E]

[0039] Figure 1 shows the sequences of several useful heterodimeric PSMAxCD28 bsAb scaffolds based on human IgGl, without cytokine sequences. Heterodimeric Fc scaffold 1 is based on human IgGl (356E / 358M allotype) and contains the L368D / K370S scuba variant and Q295E / N384D / Q418E / N421D pI variants on the first heterodimeric Fc chain, the S364K / E357Q scuba variant on the second heterodimeric Fc chain, and the E233P / L234V / L235A / G236del / S267K reduced variants on both chains. Heterodimeric Fc scaffold 2 is based on human IgG1 (356E / 358M allotype) and comprises the L368D / K370S scuba variant and the Q295E / N384D / Q418E / N421D pI variants on the first heterodimeric Fc chain, the S364K scuba variant on the second heterodimeric Fc chain, and the E233P / L234V / L235A / G236del / S267K reduced variants on both chains. Heterodimeric Fc scaffold 3 is based on human IgG1 (356E / 358M allotype) and contains the L368E / K370S scuba variant and Q295E / N384D / Q418E / N421D pI variants on the first heterodimeric Fc chain, the S364K scuba variant on the second heterodimeric Fc chain, and the E233P / L234V / L235A / G236del / S267K reduced variants on both chains. Heterodimeric Fc scaffold 4 is based on human IgG1 (356E / 358M allotype) and contains K360E / Q362E / T411E scubariant and Q295E / N384D / Q418E / N421D pI variants on the first heterodimeric Fc chain, a D401K scubariant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants on both chains.Heterodimeric Fc scaffold 5 is based on human IgG1 (356D / 358L allotype) and comprises the L368D / K370S scuba variant and the Q295E / N384D / Q418E / N421D pI variants on the first heterodimeric Fc chain, the S364K / E357Q scuba variant on the second heterodimeric Fc chain, and the E233P / L234V / L235A / G236del / S267K reduced variants on both chains. Heterodimeric Fc scaffold 6 is based on human IgG1 (356E / 358M allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an N297A variant that eliminates glycosylation on both chains. Heterodimeric Fc scaffold 7 is based on human IgG1 (356E / 358M allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an N297S variant that eliminates glycosylation on both chains. Heterodimeric Fc scaffold 8 is based on human IgG4 and comprises the L368D / K370S scuba variant and the Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, the S364K / E357Q scuba variant on the second heterodimeric Fc chain, and the S228P (S241P according to EU numbering, Kabat) variant, which reduces Fab arm exchange (as known in the art), on both chains. Heterodimeric Fc scaffold 9 is based on human IgG2 and comprises the L368D / K370S scuba variant and the Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, and the S364K / E357Q scuba variant on the second heterodimeric Fc chain.The heterodimeric Fc scaffold 10 is based on human IgG2 and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and an S267K reduced variant on both chains. Heterodimeric Fc scaffold 11 is based on human IgG1 (356E / 358M allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an M428L / N434S extended variant on both chains. Heterodimeric Fc scaffold 12 is based on human IgG1 (356E / 358M allotype) and comprises an L368D / K370S variant on the first heterodimeric Fc chain, an S364K / E357Q variant and a P217R / P229R / N276K pI variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants on both chains. Heterodimeric Fc scaffold 13 is based on human IgG1 (356E / 358M allotype) and comprises a T366W variant on the first heterodimeric Fc chain, a T366S / L368A / Y407V variant and a H435R / Y436F refined variant on the second heterodimeric Fc chain, and L234A / L235A / D265S reduced variants on both chains. Heterodimeric Fc scaffold 14 is based on human IgG1 (356E / 358M allotype) and comprises a T366W scuba variant on the first heterodimeric Fc chain, a T366S / L368A / Y407V scuba variant and a H435R / Y436F purified variant on the second heterodimeric Fc chain, and L234A / L235A / D265S reduced variants and M252Y / S254T / T256E half-life extended variants on both chains.Heterodimeric Fc scaffold 15 is based on human IgG1 (356D / 358L allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an M428L / N434S extended variant on both chains. Heterodimeric Fc scaffold 16 is based on human IgG1 (356E / 358M allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an M428L / N434A extended variant on both chains. Heterodimeric Fc scaffold 17 is based on human IgG1 (356D / 358L allotype) and comprises an L368D / K370S scuba variant and a Q295E / N384D / Q418E / N421D pI variant on the first heterodimeric Fc chain, an S364K / E357Q scuba variant on the second heterodimeric Fc chain, and E233P / L234V / L235A / G236del / S267K reduced variants and an M428L / N434A Xtend variant on both chains. Included in each of these scaffolds are sequences that are 90, 95, 98, and 99% identical (as defined herein) to the depicted sequences and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more additional amino acid substitutions (when compared to the parent human IgG1 (or IgG2 or IgG4, depending on the scaffold), as will be understood by one of skill in the art, as compared to the "parent" in the diagram, which already contains multiple amino acid modifications). That is, the depicted scaffolds can contain additional amino acid modifications (usually amino acid substitutions) in addition to or as an alternative to the skew, pI, and reduced variants contained within the scaffolds in this diagram. The scaffolds shown herein can also include deletions of the C-terminal glycine (K446_) and / or lysine (K447_).C-terminal glycine and / or lysine deletions can be intentionally engineered to reduce heterogeneity or in the context of a given bispecific format, such as a mAb-scFv format, and can also occur naturally, for example, during production and storage. [Figure 11] Exemplary sequences of heterodimeric PSMA×CD28 bsAb scaffolds for use in a 2+1 mAb-scFv format are shown. The format shown here is based on heterodimeric Fc scaffold 1 shown in Figures 10A-10E, except that it further includes G446 on monomer 1 (-) and G446 / K447 on monomer 2 (+). It should be noted that any of the additional scaffolds shown in Figures 10A-10E can be adapted for use in a 2+1 mAb-scFv format with or without K447 on one or both chains. It should be noted that these sequences can further include the M428L / N434S variant or the M252Y / S254T / T256E half-life extended variant. [Figure 12] 1 shows the sequence of "CH1" utilized in an embodiment of the PSMAxCD28 bsAb. [Figure 13] 1 shows the sequence of the "hinge" utilized in an embodiment of the PSMAxCD28 bsAb. [Figure 14] 1 shows the constant domains of the cognate light chains utilized in the subject PSMAxCD28 bsAbs that utilize the Fab binding domain. [Figure 15]The variable heavy and variable light chain sequences of an exemplary phage-derived CD28 binding domain, 1A7, and the sequence of XENP28428, an anti-CD28 mAb based on an IgG1 backbone with 1A7 and the E233P / L234V / L235A / G236del / S267K attenuation variants, are shown. CDRs are underlined, and slashes indicate the boundary(s) between the variable and constant domains. As is true for all sequences described herein that contain CDRs, the exact identification of the CDR positions varies slightly depending on the numbering used, as shown in Table 2; therefore, not only the underlined CDRs but also CDRs contained within the VH and VL domains using other numbering systems may be included herein. Furthermore, for all of the sequences in the figure, these VH and VL sequences may be used in either scFv or Fab formats. [Figure 16]

[0033] Figure 1 shows the sequence of the affinity-optimized variable heavy domain from anti-CD28 clone 1A7. It should be noted that the variable heavy domain can be paired with any of the other variable light domains shown herein, including those shown in Figures 17, 18A-18C, and 21A-21H (e.g., 1A7_H1.1_L1.71 utilized in XENP37559). [Figure 17]

[0033] Figure 1 shows the sequence of the affinity-optimized variable light domain from anti-CD28 clone 1A7. It should be noted that the variable light domain can be paired with any of the other variable light domains shown herein, including those shown in Figures 16, 18, and 21 (e.g., 1A7_H1.1_L1.71 utilized in XENP37559). [Figure 18A] The sequences of exemplary affinity-optimized 1A7 VH / VH pairs are shown. It should be noted that these pairs can be formatted as Fab or scFv. In the scFv format, these pairs can also be formatted in a VHVL or VLVH orientation. [Figure 18B]The sequences of exemplary affinity-optimized 1A7 VH / VH pairs are shown. It should be noted that these pairs can be formatted as Fab or scFv. In the scFv format, these pairs can also be formatted in a VHVL or VLVH orientation. [Figure 18C] The sequences of exemplary affinity-optimized 1A7 VH / VH pairs are shown. It should be noted that these pairs can be formatted as Fab or scFv. In the scFv format, these pairs can also be formatted in a VHVL or VLVH orientation. [Figure 19A] The consensus framework regions (FR) and complementarity determining regions (CDR) (according to Kabat) of the anti-CD28 clone 1A7 variable heavy and variable light domain variants are shown. [Figure 19B] The consensus framework regions (FR) and complementarity determining regions (CDR) (according to Kabat) of the anti-CD28 clone 1A7 variable heavy and variable light domain variants are shown. [Figure 20] 1 shows exemplary affinity engineered 1A7 VH / VL pairs and their binding affinities in the context of scFv (and in the context of a 1+1 Fab-scFv-Fc bsAb format). [Figure 21A]

[0023] Figures 1A-1C show the variable heavy and variable light chain sequences of additional CD28-binding domains utilized in the PSMAxCD28 bsAbs of the invention. As is true for all sequences herein described and containing CDRs, the exact identification of the CDR positions will vary slightly depending on the numbering used as shown in Table 2; thus, not only the underlined CDRs but also CDRs contained within the VH and VL domains using other numbering systems may be included herein. Furthermore, for all of the sequences in the figures, these VH and VL sequences may be used in either scFv or Fab formats. [Figure 21B]

[0023] Figures 1A-1C show the variable heavy and variable light chain sequences of additional CD28-binding domains utilized in the PSMAxCD28 bsAbs of the invention. As is true for all sequences herein described and containing CDRs, the exact identification of the CDR positions will vary slightly depending on the numbering used as shown in Table 2; thus, not only the underlined CDRs but also CDRs contained within the VH and VL domains using other numbering systems may be included herein. Furthermore, for all of the sequences in the figures, these VH and VL sequences may be used in either scFv or Fab formats. [Figure 21C]

[0023] Figures 1A-1C show the variable heavy and variable light chain sequences of additional CD28-binding domains utilized in the PSMAxCD28 bsAbs of the invention. As is true for all sequences herein described and containing CDRs, the exact identification of the CDR positions will vary slightly depending on the numbering used as shown in Table 2; thus, not only the underlined CDRs but also CDRs contained within the VH and VL domains using other numbering systems may be included herein. Furthermore, for all of the sequences in the figures, these VH and VL sequences may be used in either scFv or Fab formats. [Figure 21D]

[0023] Figures 1A-1C show the variable heavy and variable light chain sequences of additional CD28-binding domains utilized in the PSMAxCD28 bsAbs of the invention. As is true for all sequences herein described and containing CDRs, the exact identification of the CDR positions will vary slightly depending on the numbering used as shown in Table 2; thus, not only the underlined CDRs but also CDRs contained within the VH and VL domains using other numbering systems may be included herein. Furthermore, for all of the sequences in the figures, these VH and VL sequences may be used in either scFv or Fab formats. [Figure 21E]

[0023] Figures 1A-1C show the variable heavy and variable light chain sequences of additional CD28-binding domains utilized in the PSMAxCD28 bsAbs of the invention. As is true for all sequences herein described and containing CDRs, the exact identification of the CDR positions will vary slightly depending on the numbering used as shown in Table 2; thus, not only the underlined CDRs but also CDRs contained within the VH and VL domains using other numbering systems may be included herein. Furthermore, for all of the sequences in the figures, these VH and VL sequences may be used in either scFv or Fab formats. [Figure 21F]

[0023] Figures 1A-1C show the variable heavy and variable light chain sequences of additional CD28-binding domains utilized in the PSMAxCD28 bsAbs of the invention. As is true for all sequences herein described and containing CDRs, the exact identification of the CDR positions will vary slightly depending on the numbering used as shown in Table 2; thus, not only the underlined CDRs but also CDRs contained within the VH and VL domains using other numbering systems may be included herein. Furthermore, for all of the sequences in the figures, these VH and VL sequences may be used in either scFv or Fab formats. [Figure 21G]

[0023] Figures 1A-1C show the variable heavy and variable light chain sequences of additional CD28-binding domains utilized in the PSMAxCD28 bsAbs of the invention. As is true for all sequences herein described and containing CDRs, the exact identification of the CDR positions will vary slightly depending on the numbering used as shown in Table 2; thus, not only the underlined CDRs but also CDRs contained within the VH and VL domains using other numbering systems may be included herein. Furthermore, for all of the sequences in the figures, these VH and VL sequences may be used in either scFv or Fab formats. [Figure 21H]

[0023] Figures 1A-1C show the variable heavy and variable light chain sequences of additional CD28-binding domains utilized in the PSMAxCD28 bsAbs of the invention. As is true for all sequences herein described and containing CDRs, the exact identification of the CDR positions will vary slightly depending on the numbering used as shown in Table 2; thus, not only the underlined CDRs but also CDRs contained within the VH and VL domains using other numbering systems may be included herein. Furthermore, for all of the sequences in the figures, these VH and VL sequences may be used in either scFv or Fab formats. [Figure 22] The sequences of XENP27181, a bivalent anti-CD28 mAb based on an IgG1 backbone with the HuTN228 binding domain and E233P / L234V / L235A / G236del / S267K attenuation variants; and XENP29154, an in-house generated version of TGN1412, are shown. [Figure 23] Figure 1 shows binding of an exemplary bivalent anti-CD28 mAb based on a phage-derived clone on human PBMC. The data demonstrate that the phage approach generated a CD28-binding domain with weaker maximal binding than prior art HuTN228 (for the humanized CD28-binding domain described in Example 1A). [Figure 24A]

[0023] Figure 1 illustrates a bispecific format of the invention. The "1+1 Fab-scFv-Fc" format has a first Fab arm that binds a first antigen and a second scFv arm that binds a second antigen. The 1+1 Fab-scFv-Fc format includes a first monomer comprising a first heavy chain variable region (VH1) covalently attached (optionally via a linker) to the N-terminus of a first heterodimeric Fc scaffold, a second monomer comprising a single-chain Fv covalently attached (optionally via a linker) to the N-terminus of a second corresponding heterodimeric Fc scaffold, and a third monomer comprising a light chain variable region covalently attached to a light chain constant domain, where the light chain variable region is complementary to VH1. [Figure 24B]

[0023] Figure 1 illustrates a bispecific format of the invention. This figure illustrates a "2+1 Fab2-scFv-Fc" format having a first Fab arm and a second Fab-scFv arm, where the Fab binds a first antigen and the scFv binds a second antigen. The 2+1 Fab2-scFv-Fc format includes a first monomer comprising a first heavy chain variable region (VH1) covalently linked (optionally via a linker) to the N-terminus of a first heterodimeric Fc scaffold, a second monomer comprising a VH1 covalently linked (optionally via a linker) to a single-chain Fv that is covalently linked (optionally via a linker) to the N-terminus of a second, corresponding heterodimeric Fc scaffold, and a third monomer comprising a light chain variable region covalently linked to a light chain constant domain, where the light chain variable region is complementary to VH1. [Figure 24C]

[0023] Figure 1 illustrates a bispecific format of the invention. This shows a "1 + 1 common light chain" or "1 + 1 CLC" format, with a first Fc comprising a first Fab arm that binds a first antigen and a second Fc comprising a second Fab arm that binds a second antigen. The 1 + 1 CLC format includes a first monomer comprising VH1-CH1-hinge-CH2-CH3, a second monomer comprising VH2-CH1-hinge-CH2-CH3, and a third monomer comprising VL-CL. The VL pairs with the VH1 to form a binding domain with a first antigen-binding specificity; the VL pairs with the VH2 to form a binding domain with a second antigen-binding specificity. [Figure 24D]

[0023] Figure 1 illustrates a bispecific format of the invention. This shows a "2+1 common light chain" or "2+1 CLC" format, with a first Fc comprising two Fab arms that each bind a first antigen, and a second Fc comprising one Fab arm that binds a second antigen. The 2+1 CLC format includes a first monomer comprising VH1-CH1-hinge-VH1-CH1-hinge-CH2-CH3, a second monomer comprising VH2-CH1-hinge-CH2-CH3, and a third monomer comprising VL-CL. The VL pairs with the first and second VH1 to form a binding domain with a first antigen-binding specificity; the VL pairs with the VH2 to form a binding domain with a second antigen-binding specificity. [Figure 24E]

[0023] Figure 1 shows a bispecific format of the invention. It shows a "2+1 mAb-scFv" format having a first Fc comprising an N-terminal Fab arm that binds a first antigen and a second Fc comprising an N-terminal Fab arm that binds the first antigen and a C-terminal scFv that binds a second antigen. The 2+1 mAb-scFv format includes a first monomer comprising a VH1-CH1-hinge-CH2-CH3, a second monomer comprising a VH1-CH1-hinge-CH2-CH3-scFv, and a third monomer comprising a VL-CL. The VL pairs with the first and second VH1 to form a binding domain with binding specificity for the first antigen. [Figure 24F] 1 shows a bispecific format of the invention. Additional bispecific formats include F) dual-scFv. [Figure 24G] 1 shows a bispecific format of the invention. Additional bispecific formats include G)1-arm scFv-mAbs. [Figure 24H] 1 shows a bispecific format of the invention. Additional bispecific formats include H)scFv-mAbs. [Figure 24I] 1 illustrates a bispecific format of the invention. Additional bispecific formats include I) bispecific mAbs. [Figure 24J] 1 shows a bispecific format of the invention. Additional bispecific formats include J)1 arm center-scFv. [Figure 24K] 1 shows a bispecific format of the invention. Additional bispecific formats include K)mAb-Fv. [Figure 24L] 1 shows a bispecific format of the invention. Additional bispecific formats include L) central-Fv. [Figure 24M] 1 shows a bispecific format of the invention. Additional bispecific formats include M) trident. [Figure 25A]The variable heavy and variable light chain sequences of an exemplary PSMA-binding domain utilized in the PSMAxCD28 bsAb of the invention are shown. As is true for all sequences herein described and containing CDRs, the exact identification of the CDR positions will vary slightly depending on the numbering used as shown in Table 2; thus, not only the underlined CDRs but also CDRs contained within the VH and VL domains using other numbering systems may be included herein. Furthermore, for all of the sequences in the figure, these VH and VL sequences may be used in either scFv or Fab formats. [Figure 25B] The variable heavy and variable light chain sequences of an exemplary PSMA-binding domain utilized in the PSMAxCD28 bsAb of the invention are shown. As is true for all sequences herein described and containing CDRs, the exact identification of the CDR positions will vary slightly depending on the numbering used as shown in Table 2; thus, not only the underlined CDRs but also CDRs contained within the VH and VL domains using other numbering systems may be included herein. Furthermore, for all of the sequences in the figure, these VH and VL sequences may be used in either scFv or Fab formats. [Figure 25C] The variable heavy and variable light chain sequences of an exemplary PSMA-binding domain utilized in the PSMAxCD28 bsAb of the invention are shown. As is true for all sequences herein described and containing CDRs, the exact identification of the CDR positions will vary slightly depending on the numbering used as shown in Table 2; thus, not only the underlined CDRs but also CDRs contained within the VH and VL domains using other numbering systems may be included herein. Furthermore, for all of the sequences in the figure, these VH and VL sequences may be used in either scFv or Fab formats. [Figure 25D]The variable heavy and variable light chain sequences of an exemplary PSMA-binding domain utilized in the PSMAxCD28 bsAb of the invention are shown. As is true for all sequences herein described and containing CDRs, the exact identification of the CDR positions will vary slightly depending on the numbering used as shown in Table 2; thus, not only the underlined CDRs but also CDRs contained within the VH and VL domains using other numbering systems may be included herein. Furthermore, for all of the sequences in the figure, these VH and VL sequences may be used in either scFv or Fab formats. [Figure 25E] The variable heavy and variable light chain sequences of an exemplary PSMA-binding domain utilized in the PSMAxCD28 bsAb of the invention are shown. As is true for all sequences herein described and containing CDRs, the exact identification of the CDR positions will vary slightly depending on the numbering used as shown in Table 2; thus, not only the underlined CDRs but also CDRs contained within the VH and VL domains using other numbering systems may be included herein. Furthermore, for all of the sequences in the figure, these VH and VL sequences may be used in either scFv or Fab formats. [Figure 26A] The variable heavy and variable light chain sequences of additional PSMA-binding domains utilized in the PSMAxCD28 bsAbs of the invention are shown. As is true for all sequences herein described and containing CDRs, the exact identification of the CDR positions will vary slightly depending on the numbering used as shown in Table 2; thus, not only the underlined CDRs but also CDRs contained within the VH and VL domains using other numbering systems may be included herein. Furthermore, for all of the sequences in the figures, these VH and VL sequences may be used in either scFv or Fab formats. [Figure 26B]The variable heavy and variable light chain sequences of additional PSMA-binding domains utilized in the PSMAxCD28 bsAbs of the invention are shown. As is true for all sequences herein described and containing CDRs, the exact identification of the CDR positions will vary slightly depending on the numbering used as shown in Table 2; thus, not only the underlined CDRs but also CDRs contained within the VH and VL domains using other numbering systems may be included herein. Furthermore, for all of the sequences in the figures, these VH and VL sequences may be used in either scFv or Fab formats. [Figure 27] Figure 1 shows A) a classical T cell / APC interaction and B) replication of the classical T cell / APC interaction by combining a CD3 bispecific antibody with a CD28 bispecific antibody. In classical T cell / APC interactions, there is a first signal (signal 1) provided by TCR reactivity with peptide-MHC and a second signal (signal 2) provided by CD28 cross-linking by CD80 / CD86 expressed on the APC, which together are sufficient to activate the T cell. In contrast, treatment with a CD3 bispecific provides only the first signal. A CD28 signal can be provided by a CD28 bispecific with the intention of promoting activation and proliferation through CD28 costimulation. In some embodiments, TAA1 and TAA2 can be different antigens. In some embodiments, TAA1 and TAA2 can be the same antigen but different epitopes. In some embodiments, TAA1 and TAA2 can be the same antigen and the same epitope. [Figure 28A] 1 shows the sequence of an exemplary PSMAxCD3 bsAb that can be combined with the PSMAxCD28 bsAb of the present invention. [Figure 28B] 1 shows the sequence of an exemplary PSMAxCD3 bsAb that can be combined with the PSMAxCD28 bsAb of the present invention. [Figure 28C] 1 shows the sequence of an exemplary PSMAxCD3 bsAb that can be combined with the PSMAxCD28 bsAb of the present invention. [Figure 29]The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29B] The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29C]The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29D] The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29E]The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29F] The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29G]The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29H] The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29I]The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29J] The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29K]The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29L] The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29M]The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29N] The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29O]The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29P] The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29Q]The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29R] The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29S]The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29T] The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29U]The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29V] The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29W]The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29X] The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29Y]The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29Z] The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29AA]The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29BB] The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29CC]The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29DD] The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29EE]The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29FF] The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29GG]The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29HH] The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29II]The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29JJ] The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29KK]The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29LL] The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc domains; the inclusion of M428L / N434S results in a longer half-life in serum. [Figure 29MM]The sequences of exemplary PSMAxCD28 bsAbs in a 1+1 Fab-scFv-Fc format using platform X are shown. While these sequences utilize platform X, they may also use platform J or any other suitable scaffold, including those shown in Figures 10A-10E. CDRs are underlined, and slashes indicate the boundary(s) between the variable region, Fc region, and constant domain. It should be noted that PSMAxCD28 bsAbs may utilize variable region, Fc region, and constant domain sequences that are 90, 95, 98, or 99% identical (as defined herein) and / or contain 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acid substitutions. Additionally, each sequence outlined herein may include or exclude the M428L / N434S variant in one or, preferably, both Fc dom...

Claims

1. A bispecific anti-PSMA x anti-CD28 antibody, a) a first monomer having the amino acid sequence of SEQ ID NO: 342; b) a second monomer having the amino acid sequence of SEQ ID NO: 343; and c) a light chain having the amino acid sequence of SEQ ID NO: 344 A bispecific anti-PSMA x anti-CD28 antibody comprising:

2. 1. A nucleic acid composition comprising: a) a first nucleic acid encoding a first monomer; b) a second nucleic acid encoding a second monomer; and c) a third nucleic acid encoding a light chain wherein the first monomer, the second monomer, and the light chain are the first monomer, the second monomer, and the light chain of claim 1, respectively.

3. A vector composition comprising: a) a first vector comprising a first nucleic acid encoding a first monomer; b) a second vector comprising a second nucleic acid encoding a second monomer; and c) a third vector comprising a third nucleic acid encoding a light chain. wherein the first monomer, the second monomer, and the light chain are the first monomer, the second monomer, and the light chain of claim 1, respectively.

4. The vector composition described in claim 3, wherein the first vector, the second vector, and the third vector are each an expression vector.

5. A vector comprising: a) a first nucleic acid encoding a first monomer; b) a second nucleic acid encoding a second monomer; and c) a third nucleic acid encoding a light chain wherein the first monomer, the second monomer, and the light chain are the first monomer, the second monomer, and the light chain of claim 1, respectively.

6. The vector described in claim 5, wherein the vector is an expression vector.

7. A host cell comprising the nucleic acid composition of claim 2.

8. The host cell described in claim 7, wherein the host cell is a CHO cell.

9. A method for producing a bispecific antibody, the method comprising culturing a cell described in claim 7 or 8 under conditions in which the bispecific antibody is expressed, and recovering the bispecific antibody.

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