Antigen-binding polypeptides, antigen-binding polypeptide complexes, and methods of using same

JP2024537828A5Pending Publication Date: 2026-01-23MODEX THERAPEUTICS INC
View PDF 0 Cites 0 Cited by

Patent Information

Application Number
JP2024519823
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Priority Date
2021-12-21
Filing Date
2022-09-28
Publication Date
2026-01-23

AI Technical Summary

Technical Problem

The development of multispecific antibodies, particularly for HIV treatment, is challenging due to the need for multiple genes or plasmids for cell line development, which can lead to mismatched heavy and light chains, reducing product yield and increasing heterogeneity, and existing therapies face issues with drug resistance and toxicity.

Method used

Development of antigen-binding polypeptides and polypeptide complexes with specific variable region combinations and linkers to enhance binding affinity and efficacy, simplifying manufacturing and reducing heterogeneity.

Benefits of technology

The proposed polypeptides and complexes improve binding selectivity and efficacy, offering a less frequent treatment regimen with reduced toxicity and drug resistance, suitable for HIV treatment and prevention.

✦ Generated by Eureka AI based on patent content.

Smart Images

  • Figure 2023056314000001
    Figure 2023056314000001
  • Figure 2023056314000002
    Figure 2023056314000002
  • Figure 2023056314000003
    Figure 2023056314000003
Patent Text Reader

Abstract

Disclosed are antigen-binding polypeptides and antigen-binding polypeptide complexes (e.g., antibodies and antigen-binding fragments thereof) having certain structural characteristics. Also disclosed are polynucleotides and vectors encoding such polypeptides and polypeptide complexes, host cells, chimeric antigen receptors (CARs), immune cells, pharmaceutical compositions, and kits containing such polypeptides and polypeptide complexes, and methods of using such polypeptides and polypeptide complexes.
Need to check novelty before this filing date? Find Prior Art

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63 / 249,722, filed September 29, 2021, U.S. Provisional Application No. 63 / 249,794, filed September 29, 2021, U.S. Provisional Application No. 63 / 249,833, filed September 29, 2021, U.S. Provisional Application No. 63 / 249,919, filed September 29, 2021, U.S. Provisional Application No. 63 / 291,305, filed December 17, 2021, and U.S. Provisional Application No. 63 / 292,382, filed December 21, 2021, all of which are incorporated by reference in their entirety.

[0002] Reference to an electronically submitted sequence listing The contents of the electronically submitted sequence listing (Name: 4850_005PC01_Seqlisting_ST26; Size: 1,215,029 bytes, and Creation Date: September 26, 2022) are incorporated herein by reference in their entirety.

[0003] Field The present disclosure relates to antigen-binding polypeptides and antigen-binding polypeptide complexes (e.g., antibodies and antigen-binding fragments thereof) having certain structural characteristics. The disclosure also relates to polynucleotides and vectors encoding such polypeptides and polypeptide complexes, host cells containing such polypeptides and polypeptide complexes, chimeric antigen receptors (CARs), immune cells, pharmaceutical compositions, and kits, as well as methods of using such polypeptides and polypeptide complexes. [Background technology]

[0004] background Immunotherapy is the treatment of diseases by activating or suppressing the immune system. In recent years, immunotherapy has become of great interest to researchers and clinicians, especially in its potential to treat cancer and infectious diseases. Therapeutic antibodies are an important type of immunotherapy. Therapeutic antibodies can be monospecific, meaning they have specificity for one antigen or epitope. Therapeutic antibodies have also been engineered to have specificity for two different antigens or epitopes (i.e., bispecific antibodies) or multiple different antigens or epitopes (trispecific antibodies, tetraspecific antibodies, etc.). In addition, monospecific antibodies, bispecific antibodies, and multispecific antibodies have been combined to form multitargeting strategies for treating complex human diseases such as cancer and infectious diseases.

[0005] However, the development of therapeutic antibodies can be challenging, especially in manufacturing and later stages of development. For example, the production of bispecific or multispecific antibodies often requires multiple genes or plasmids for cell line development. These multiple genes or plasmids must be delivered to the same cell to produce the correct molecule. Furthermore, bispecific and multispecific antibodies may have mismatched heavy and light chains, which can reduce product yields, increase cell line colony screening workload, and result in product heterogeneity.

[0006] A need exists for multispecific and multifunctional antigen-binding polypeptides and antigen-binding polypeptide complexes that can bind to specific combinations of target molecules for selectivity or amplification / neutralization, bring together two or more cell types, bring together targets to deliver activating signals, modify the disease microenvironment, and enhance binding affinity for improved efficacy. The present invention fulfills this unmet need.

[0007] Additionally, human immunodeficiency virus (HIV) imposes a major infectious disease burden worldwide with enormous medical and economic impact. Globally, approximately 38 million people are infected with HIV, and more than 30 million people suffer from acquired immunodeficiency syndrome (AIDS), a chronic condition of weakened immune system caused by HIV infection. "Global Health Sector Strategy On HIV-2016-2021 - Towards Ending AIDS," World Health Organization, June 2016 (Non-Patent Document 1). There are two major forms of HIV: HIV-1 and HIV-2. HIV-1 is the more common form worldwide, while HIV-2 is less pathogenic and is primarily limited to West Africa.

[0008] The major structural proteins of HIV are Gag, Pol, and Env. Gag (group-specific antigen) is a structural protein of the viral core. Pol is a polyprotein containing enzymes important for viral replication: protease (PR), reverse transcriptase (RT), and integrase (IN). Env (envelope) encodes the glycoprotein that forms the outer envelope of the virus. Env is synthesized as a precursor glycoprotein, gp160, which is then processed into gp120 and gp41. Env interacts with the primary receptor, CD4, and co-receptors (such as the chemokine receptor CCR5) to fuse the viral and target cell membranes.

[0009] The genetic heterogeneity and glycan shield of Env resist the development of natural immunity against HIV, posing a challenge to conventional vaccine development and prompting the search for alternative approaches to HIV prevention, one of the highest global health priorities.

[0010] Despite the availability of a significant selection of anti-HIV / AIDS drugs, HIV patients still face the daily challenges of taking multiple medications in rigorous regimens. Inevitably, most patients endure the consequences of the emergence of drug-resistant viral variants and develop other health problems, such as cardiovascular disease, kidney disease, diabetes, bone disease, liver disease, and cognitive impairment, from the toxicity of long-term anti-HIV medications. Alternative treatment options are urgently needed for HIV / AIDS patients.

[0011] Broadly neutralizing HIV-1 antibodies (bnAbs) are antibodies that neutralize multiple HIV-1 virus strains. bnAbs target conserved epitopes on the virus, meaning that the targeted epitopes are more likely to remain even when the virus mutates. Therefore, bnAbs have recently been investigated for the treatment and prevention of HIV / AIDS. Human clinical studies have revealed two key factors for the efficacy of bnAbs. First, there is a need to exceed the minimum effective dose or trough level of circulating bnAbs to prevent infection. Second, there is a need to prevent the emergence of viral escape through resistance mutations.

[0012] Early human clinical studies using bnAbs demonstrated the feasibility and safety of this approach, with transient reductions in viral load and acceptable tolerability and immunogenicity. Burton et al., Annu. Rev. Immunol. 34:635-659 (2016) (Non-Patent Document 2), Mascola et al., Immunol. Rev. 254:225-244 (2013) (Non-Patent Document 3), Wu et al., Science. 329:856-861 (2010) (Non-Patent Document 4). However, resistant HIV strains rapidly emerged after treatment with individual bnAbs in vitro and in vivo. More recently, a phase II clinical trial using the VRC01 bnAb emphasized the importance of maintaining adequate circulating antibody levels to reduce acquisition rates, suggesting that combination antibody therapies that improve efficacy and minimize escape mutations will be required for effective prevention. Corey et al., N. Engl. J. Med. 384:1003-1014 (2021) (Non-patent Document 5).

[0013] Multispecific antibodies address the limitations of bnAbs by providing a single antibody type that recognizes multiple independent binding sites on the HIV-1 envelope protein. Xu et al., Science. 358(6359):85-90(2017) (Non-Patent Document 6). Treatment with multispecific antibodies also ensures that independent binding specificities maintain the same pharmacokinetics, while treatment with multiple single-targeting antibodies results in different antibody half-lives that decline at different rates. Furthermore, multispecific antibodies simplify manufacturing and administrative procedures by using a single product for clinical development instead of a combination of multiple products.

[0014] Thus, multispecific anti-HIV antibodies provide an important technology platform for developing neutralizing antibody-based therapeutics for treating HIV / AIDS, offering a class of drugs with low long-term toxicity and significantly less frequent treatment regimens. Multispecific antibodies also complement existing drugs by using an HIV target that is completely different from current standard-of-care HIV / AIDS drugs, offering patients an alternative for disease control and health management. Multispecific antibodies may also offer a meaningful approach to HIV prevention, where no effective HIV vaccine currently exists.

[0015] In addition, the development of therapeutic antibodies can be challenging, especially in manufacturing and later stages of development. For example, the production of multispecific antibodies often requires multiple genes or plasmids for cell line development. These multiple genes or plasmids must be delivered to the same cell to produce the correct molecule. Furthermore, multispecific antibodies may have mismatched heavy and light chains, which can reduce product yields, increase cell line colony screening workload, and result in product heterogeneity.

[0016] Thus, there is a need for multispecific and multifunctional antibodies, antigen-binding polypeptides, and antigen-binding polypeptide complexes that can bind to HIV proteins for selectivity or amplification / neutralization, bring together two or more cell types, bring together targets to deliver activation signals, modify the HIV microenvironment, and enhance binding affinity to improve efficacy. The present invention fulfills this unmet need. [Prior art documents] [Non-patent literature]

[0017] [Non-Patent Document 1] “Global Health Sector Strategy On HIV-2016-2021-Towards Ending AIDS,” World Health Organization, June 2016

Non-Patent Document 2

Non-Patent Document 3

Non-Patent Document 4

Non-Patent Document 5

Non-Patent Document 6

Summary of the Invention

[0018] Summary Provided herein are VL1-VL2-VL3-VH3-VH2-VH1, VH1-VH2-VH3-VL3-VL2-VL1, VL1-VH2-VL3-VH3-VL2-VH1, VH1-VL2-VH3-VL3-VH2-VL1, VL1-VL2-VH3-VL3-VH2-VL1, VL1-VL2-VH3-VL3-VH2-VH1, VH1-VH2-VL3-VH3-VL2-VL1, VL1-VH2-VH3-VL3-VL2-VH1, VH1-VH2-VL3-VH3-VL2-VL1, VL1-VH2-VH3-VL3-VL2-VH1, VH1-VH2-VL3-VH3-VL2-VL1 L2-VL3-VH3-VH2-VL1, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5- VL1, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1, VL1-L1-VL2-L 2-VH3-L3-VL3-L4-VH2-L5-VH1, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1, or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1, wherein VL1 is a first VL1 is a first immunoglobulin light chain variable region, VL2 is a second immunoglobulin light chain variable region, VL3 is a third immunoglobulin light chain variable region, VH1 is a first immunoglobulin heavy chain variable region, VH2 is a second immunoglobulin heavy chain variable region, VH3 is a third immunoglobulin heavy chain variable region, and L1, L2, L3, L4, and L5 are amino acid linkers.

[0019] Provided herein is an antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide, wherein the first polypeptide is selected from the group consisting of VL1-VL2-VL3-VH3-VH2-VH1, VH1-VH2-VH3-VL3-VL2-VL1, VL1-VH2-VL3-VH3-VL2-VH1, VH1-VL2-VH3-VL3-VH2-VL1, VL1-VL2-VH3-VL3-VH2-VH1, VL1-VL2-VH3-VL3-VH2-VH1, VH1-VH2-VL3-VH3-VL2-VL1, VL1-VH2-VH3-VL3-VL2-VH1, VL1-VH2-VL3-VH3-VL2-VL1, VL1-VH2-VH3-VL3-VL2-VH1, VH1-VL2-VL3-VH 3-VH2-VL1, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1, VH1-L1-VH2-L 2-VH3-L3-VL3-L4-VL2-L5-VL1, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5- VH1, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1, VL1-L1-VL2-L2-VH3-L 3-VL3-L4-VH2-L5-VH1, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1, VL1 -L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1, or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1, and the second polypeptide is VL4-VH4, VH4-VL4, VL4-L6-VH4, VH4-L6-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-L6-VL5-L7-VH5-L8-VH4, VH4-L6-VH5-L7-VL5-L8-VL4, VL4-VL5-VL6-VH6-VH5-VH4, V H4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL 6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4- VH5-VH6-VL6-VL5-VH4, VH4-VL5-VL6-VH6-VH5-VL4, VL4-L6-VL5-L7-VL6- L8-VH6-L9-VH5-L10-VH4, VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4,VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4, VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-V L4, VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4, VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10 -VL4, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4, or VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4, where VL1 is a first immunoglobulin light chain variable region and VL2 is a second immunoglobulin light chain variable region; an antigen-binding polypeptide complex, wherein L3 is a third immunoglobulin light chain variable region, VL4 is a fourth immunoglobulin light chain variable region, VL5 is a fifth immunoglobulin light chain variable region, VL6 is a sixth immunoglobulin light chain variable region, VH1 is a first immunoglobulin heavy chain variable region, VH2 is a second immunoglobulin heavy chain variable region, VH3 is a third immunoglobulin heavy chain variable region, VH4 is a fourth immunoglobulin heavy chain variable region, VH5 is a fifth immunoglobulin heavy chain variable region, VH6 is a sixth immunoglobulin heavy chain variable region, and L1, L2, L3, L4, L5, L6, L7, L8, L9, and L10 are amino acid linkers.

[0020] Provided herein is an antigen-binding polypeptide having a structure represented by VL1-VL2-VL3-VH3-VH2-VH1-Fc, VH1-VH2-VH3-VL3-VL2-VL1-Fc, VL1-VH2-VL3-VH3-VL2-VH1-Fc, VH1-VL2-VH3-VL3-VH2-VL1-Fc, VL1-VL2-VH3-VL3-VH2-VH1-Fc, VH1-VH2-VL3-VH3-VL2-VL1-Fc, VL1-VH2-VH3-VL3-VL2-VH1-Fc, VH1-VL2-VL3-VH3-VH2-VL1-Fc, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-Fc, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-Fc, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-Fc, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-Fc, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-Fc, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-Fc, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-Fc, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-Fc, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-Fc, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-Fc, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-Fc, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-Fc, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-Fc, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-Fc, VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-Fc, or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-Fc, wherein VL1 is a first immunoglobulin light chain variable region, VL2 is,is a second immunoglobulin light chain variable region, VL3 is a third immunoglobulin light chain variable region, VH1 is a first immunoglobulin heavy chain variable region, VH2 is a second immunoglobulin heavy chain variable region, VH3 is a third immunoglobulin heavy chain variable region, Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge, and L1, L2, L3, L4, L5, and L6 are amino acid linkers.

[0021] What is provided in this specification are VL1-VL2-VL3-VH3-VH2-VH1-Fc-Fc, VH1-VH2-VH3-VL3-VL2-VL1-Fc-Fc, VL1-VH2-VL3-VH3-VL2-VH1-Fc-Fc, VH1-VL2-VH3-VL3-VH2-VL1-Fc-Fc, VL1-VL2-VH3-VL3-VH2-VH1-Fc-Fc, VH1-VH2-VL3-VH3-VL2-VL1-Fc-Fc, VL1-VH2-VH3-VL3-VL2-VH1-Fc-Fc, VH1-VL2-VL3-VH3-VH2-VL1-Fc-Fc, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-Fc-Fc, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-Fc-Fc, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-Fc-L7-Fc, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-Fc-Fc, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-Fc-Fc, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-Fc-L7-Fc, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-Fc-Fc, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-Fc-Fc, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-Fc-L7-Fc, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-Fc-Fc, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-Fc-Fc, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-Fc-L7-Fc, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-Fc-Fc, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-Fc-Fc, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-Fc-L7-Fc,VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-Fc-Fc, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-Fc-Fc , VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-Fc-L7-Fc, L1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-Fc -Fc, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-Fc-Fc, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L 6-Fc-L7-Fc, VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-Fc-Fc, VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL and an antigen-binding polypeptide having a structure represented by VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-Fc-Fc, or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-Fc-L7-Fc, wherein VL1 is a first immunoglobulin light chain variable region, VL2 is a second immunoglobulin light chain variable region, and VL3 is a third immunoglobulin light chain variable region; and VH1 is a first immunoglobulin light chain variable region, VL2 is a second immunoglobulin light chain variable region, and VL3 is a third immunoglobulin light chain variable region; VH1 is a second immunoglobulin heavy chain variable region, VH2 is a second immunoglobulin heavy chain variable region, VH3 is a third immunoglobulin heavy chain variable region, Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge, and L1, L2, L3, L4, L5, L6, and L7 are amino acid linkers.

[0022] Provided herein is an antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide, wherein the first polypeptide is selected from the group consisting of VL1-VL2-VL3-VH3-VH2-VH1-Fc, VH1-VH2-VH3-VL3-VL2-VL1-Fc, VL1-VH2-VL3-VH3-VL2-VH1-Fc, VL1-VH2-VL3-VH3-VL2-VH1-Fc, VH1-VL2-VH3-VL3-VH2-VL1-Fc, VL1-VL2-VH3-VL3-VH2-VH1-Fc, VL1-VL2-VH3-VL3-VH2-VH1-Fc, VL1-VH2-VL3-VH3-VL2-VH1-Fc, VL1-VH2-VL3-VH3-VL2-VH1-Fc, VL1-VH2-VH3-VL ... H1-Fc, VH1-VL2-VL3-VH3-VH2-VL1-Fc, VL1-L1-VL2-L2-VL3-L3-VH3-L4-V H2-L5-VH1-Fc, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-Fc, VH1- L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-Fc, VH1-L1-VH2-L2-VH3-L3-VL3 -L4-VL2-L5-VL1-L6-Fc, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-Fc , VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-Fc, VH1-L1-VL2-L2-VH 3-L3-VL3-L4-VH2-L5-VL1-Fc, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-V L1-L6-Fc, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-Fc, VL1-L1-VL2- L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-Fc, VH1-L1-VH2-L2-VL3-L3-VH3-L4- VL2-L5-VL1-Fc, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-Fc, VL1 -L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-Fc, VL1-L1-VH2-L2-VH3-L3-VL 3-L4-VL2-L5-VH1-L6-Fc, VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-F c, or has a structure represented by VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-Fc,The second polypeptide is Fc, VL4-VH4-Fc, VH4-VL4-Fc, VL4-L7-VH4-Fc, VH4-L7-VH4-Fc, VH4-L7-VH4-Fc, VH4-L7-VH4-L8-Fc, VH4-L7-VH4-L8-Fc, VL4-CL-VH4-CH1-Fc, VH4-CL-VL4-CH1-Fc, VL4-CH1-VH4-CL-Fc, VH4-CH1-VH4-CL-Fc, VH4-CH1-VL4-CL-Fc, VL4-L7-CL-L8-VH4-L9-CH1-Fc, VL4-L7-CL-L8-VH4-L9-CH1-Fc, VH4-L7-CL-L8-VH4-L9-CH1-Fc, VH4-L7-CL-L8-VH4-L9-CH1-L10-Fc, VH4-L7-CL-L8-VL4-L9-C H1-Fc, VH4-L7-CL-L8-VL4-L9-CH1-L10-Fc, VL4-L7-CH1-L8-VH4-L9-CL-Fc, VL4-L7-CH1-L8-VH4-L9-CL-Fc, VL4-L7-CH1-L8-VH4-L9-CL-L10-Fc, VH4-L7-CH1-L8-VL4-L9-CL-Fc, VH4-L7-CH1-L8-VL4-L9-CL-L10-Fc, VL4-VL5-VH5-VH4-Fc, VH4-VH5-VL5-VL4-Fc, VL4-L7-VL5-L8-VH5-L9-VL4-Fc, VL 4-L7-VL5-L8-VH5-L9-VH4-L10-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-L10-Fc, VL4-VL5-VL6-VH6-VH5-VH4-Fc, VH4-VH5-VH6-VL6-VL5-VL4-Fc, VL4-VH5-VL6-VL6-VL5-VL4-Fc, VL4-VH5-VL6-VL6-VL5-VH4-Fc, VH4-VL5-VH6-VL6-VL4-Fc, VL4-VL5-VH6-VL6-VL4-Fc, VL4-VL5-VH6-VL6-VL5-VH c. VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-Fc、VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-Fc、VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-Fc、VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-Fc, VL4-L7-VH5-L8-VH6- L9-VL6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11 -VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-L12-Fc, VH4-L7 -VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VL6-L9 -VH6-L10-VL5-L11-VH4-L12-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L 11-VL4-L12-Fc, VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8- VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc, or VH4-L7-VL5-L8-VL6-L9-VH6- and VL1 is a first immunoglobulin light chain variable region, VL2 is a second immunoglobulin light chain variable region, VL3 is a third immunoglobulin light chain variable region, VL4 is a fourth immunoglobulin light chain variable region, VL5 is a fifth immunoglobulin light chain variable region, and VL6 is a sixth immunoglobulin light chain variable region, VH1 is a first immunoglobulin heavy chain variable region, VH2 is a second immunoglobulin heavy chain variable region, and VH3 is a third immunoglobulin light chain variable region. VH4 is a fourth immunoglobulin heavy chain variable region, VH5 is a fifth immunoglobulin heavy chain variable region, VH6 is a sixth immunoglobulin heavy chain variable region, Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge, CH1 is heavy chain constant region 1, CL is a light chain constant region, and L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, and L12 are amino acid linkers;It is an antigen-binding polypeptide complex.

[0023] Provided herein are VL1-VL2-VL3-VH3-VH2-VH1-CH1-CL, VL1-VL2-VL3-VH3-VH2-VH1-CL-CH1, VH1-VH2-VH3-VL3-VL2-VL1-CH1-CL, VH1-VH2-VH3-VL3-VL2-VL1-CL-CH1, VL1-VH2-VL3-VH3-VL2-VH1-CH1-CL, VL1-VH2-VL3-VH3-VL2-VH1-CL-CH1, VH1-VL2-VH3-VL3-VH2-VL1-CH1-CL, VH1-VL2-VH3-VL3-VH2-VL1-CL-CH1, VL1-VL2-VH3-VL3-VH2-VH1-CH1-CL, VL1-VL2-VH3-VL3-VH2-VH1-CL-CH1, VH1-VH2-VL3-VH3-VL2-VL1-CH1-CL, VH1-VH2-VL3-VH3-VL2-VL1-CL-CH1, VL1-VH2-VH3-VL3-VL2-VH1-CH1-CL, VL1-VH2-VH3-VL3-VL2-VH1-CL-CH1, VH1-VL2-VL3-VH3-VH2-VL1-CH1-CL, VH1-VL2-VL3-VH3-VH2-VL1-CL-CH1, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CH1-CL, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CH1-CL, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CL-CH1, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CL-CH1, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CL-L7-CH1, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CH1-CL, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CH1-CL, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CH1-L7-CL, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CL-CH1, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CL-CH1,VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CH1-CL, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CH1-CL, VL1-L1-VH2-L2-VL3-L3-VH3-L4 -VL2-L5-VH1-L6-CH1-L7-CL、VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CL-CH1、VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CL-CH1、VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CH1-CL、VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CH1-CL、VH1-L1-VL2-L2-VH3-L3-VL3-L4-V H2-L5-VL1-L6-CH1-L7-CL, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CL-CH1, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CL-CH1, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CL-L7-CH1, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CH1-CL, VL1-L1-VL2-L2-VH3-L3-VL3-L4- VH2-L5-VH1-L6-CH1-CL, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CH1-L7-CL, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CL-CH1, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CL-CH1, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CL-L7-CH1, VH1-L1-VH2-L2-VL3-L3-VH3 -L4-VL2-L5-VL1-CH1-CL、VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CH1-CL、VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CH1-L7-CL、VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CL-CH1, VH1-L1-VH2-L2-VL 3-L3-VH3-L4-VL2-L5-VL1-L6-CL-CH1, VH1-L1-VH2-L2-VL3-L3-VH3-L4-V L2-L5-VL1-L6-CL-L7-CH1, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1- L6-CL, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CH1-CL, VL1-L1-VH2 -L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CH1-CL, VL1-L1-VH2-L2-VH3-L3-VL 3-L4-VL2-L5-VH1-L6-CH1-L7-CL, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L 5-VH1-CL-CH1, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CL-CH1, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CL-L7-CH1, VH1-L1-VL2 -L2-VL3-L3-VH3-L4-VH2-L5-VL1-CH1-CL, VH1-L1-VL2-L2-VL3-L3-VH3-L 4-VH2-L5-VL1-L6-CH1-CL, VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1- L6-CH1-L7-CL, VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CL-CH1, VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CL-CH1, or VH1-L1-VL2-L2 -VL3-L3-VH3-L4-VH2-L5-VL1-L6-CL-L7-CH1, wherein VL1 is a first immunoglobulin light chain variable region, VL2 is a second immunoglobulin light chain variable region, VL3 is a third immunoglobulin light chain variable region, VH1 is a first immunoglobulin heavy chain variable region, VH2 is a second immunoglobulin heavy chain variable region, VH3 is a third immunoglobulin heavy chain variable region, CH1 is immunoglobulin heavy chain constant region 1, and CL isAn immunoglobulin light chain constant region, an antigen-binding polypeptide, wherein L1, L2, L3, L4, L5, L6, and L7 are amino acid linkers.

[0024] Provided herein are antigen-binding polypeptide complexes comprising a first polypeptide and a second polypeptide, wherein the first polypeptide is selected from the group consisting of VL1-VL2-VL3-VH3-VH2-VH1-CH1, VL1-VL2-VL3-VH3-VH2-VH1-CL, VL1-VL2-VL3-VH3-VH2-VH1-CH1-CL, VL1-VL2-VL3-VH3-VH2-VH1-CL-CH1, VH1-VH2-VH3-VL3-VL2-VL1-CH1, VH1-VH2-VH3-VL3-VL2-VL1-CL ...CL, VH1 L3-VL2-VL1-CH1-CL, VH1-VH2-VH3-VL3-VL2-VL1-CL-CH1, VL1-VH2-VL3-V H3-VL2-VH1-CH1, VL1-VH2-VL3-VH3-VL2-VH1-CL, VL1-VH2-VL3-VH3-VL2-V H1-CH1-CL, VL1-VH2-VL3-VH3-VL2-VH1-CL-CH1, VH1-VL2-VH3-VL3-VH2-V L1-CH1, VH1-VL2-VH3-VL3-VH2-VL1-CL, VH1-VL2-VH3-VL3-VH2-VL1-CH1-C L, VH1-VL2-VH3-VL3-VH2-VL1-CL-CH1, VL1-VL2-VH3-VL3-VH2-VH1-CH1, V L1-VL2-VH3-VL3-VH2-VH1-CL, VL1-VL2-VH3-VL3-VH2-VH1-CH1-CL, VL1-VL 2-VH3-VL3-VH2-VH1-CL-CH1, VH1-VH2-VL3-VH3-VL2-VL1-CH1, VH1-VH2-V L3-VH3-VL2-VL1-CL, VH1-VH2-VL3-VH3-VL2-VL1-CH1-CL, VH1-VH2-VL3-VH 3-VL2-VL1-CL-CH1, VL1-VH2-VH3-VL3-VL2-VH1-CH1, VL1-VH2-VH3-VL3-V L2-VH1-CL, VL1-VH2-VH3-VL3-VL2-VH1-CH1-CL, VL1-VH2-VH3-VL3-VL2-VH 1-CL-CH1, VH1-VL2-VL3-VH3-VH2-VL1-CH1, VH1-VL2-VL3-VH3-VH2-VL1-CL , VH1-VL2-VL3-VH3-VH2-VL1-CH1-CL, VH1-VL2-VL3-VH3-VH2-VL1-CL-CH1,VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CH1, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CH1, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L 5-VH1-CL、VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CL、VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CH1-CL、VL1-L1-VL2-L2-VL3-L3-VH 3-L4-VH2-L5-VH1-L6-CH1-CL、VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CH1-L7-CL、VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CL-CH1 、VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CL-CH1、VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CL-L7-CH1、VH1-L1-VH2-L2-VH3-L3- VL3-L4-VL2-L5-VL1-CH1, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CH1, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CL, VH1-L1-VH2-L2 -VH3-L3-VL3-L4-VL2-L5-VL1-L6-CL、VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CH1-CL、VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CH1 -CL、VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CH1-L7-CL、VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CL-CH1、VH1-L1-VH2-L2-VH3-L3- VL3-L4-VL2-L5-VL1-L6-CL-CH1, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CL-L7-CH1, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CH1VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CH1, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CL, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5- VH1-L6-CL, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CH1-CL, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CH1-CL, VL1-L1-VH2-L2-VL3- L3-VH3-L4-VL2-L5-VH1-L6-CH1-L7-CL、VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CL-CH1、VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-C L-CH1, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CL-L7-CH1, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CH1, VH1-L1-VL2-L2-VH3-L3-VL 3-L4-VH2-L5-VL1-L6-CH1, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CL, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CL, VH1-L1-VL2-L2 -VH3-L3-VL3-L4-VH2-L5-VL1-CH1-CL, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CH1-CL, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CH1-L7-CL, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CL-CH1, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CL-CH1, VH1-L1-VL2-L2-VH3 -L3-VL3-L4-VH2-L5-VL1-L6-CL-L7-CH1、VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CH1、VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CH1、VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CL、VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CL、VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5- VH1-CH1-CL, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CH1-CL, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CH1-L7-CL, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CL-CH1, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CL-CH1, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1- L6-CL-L7-CH1, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CH1, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CH1, VH1-L1-VH2-L2-VL3-L3- VH3-L4-VL2-L5-VL1-CL, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CL, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CH1-CL, VH1-L1-VH2 -L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CH1-CL、VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CH1-L7-CL、VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CL-CH1、VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CL-CH1、VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CL-L7-CH1、VL1-L1-V H2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CH1, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CH1, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CLVL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CL, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CH1-CL, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2- L5-VH1-L6-CH1-CL, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CH1-L7-CL, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CL-CH1, VL1-L1-VH 2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CL-CH1、VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CL-L7-CH1、VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2 -L5-VL1-CH1、VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CH1、VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CL、VH1-L1-VL2-L2-VL3-L3-VH3 -L4-VH2-L5-VL1-L6-CL、VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CH1-CL、VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CH1-CL、VH1-L1- VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CH1-L7-CL, VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CL-CH1, VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L 5-VL1-L6-CL-CH1、またはVH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-C L-L7-CH1 4-CH1-CL、VL4-VH4-CL-CH1、VH4-VL4-CH1、VH4-VL4-CL、VH4-VL4-CH1-CL、 VH4-VL4-CL-CH1、VL4-L8-VH4-CH1、VL4-L8-VH4-CL、VL4-L8-VH4-CH1-CL、VL4-L8-VH4-CL-CH1、VH4-L8-VL4-CH1、VH4-L8-VL4-CL、VH4-L8-VH4-CH1-CL、VH4-L8-VH4-CL-CH1、VL4-VL5-VH5-VH4-CH1、VL4-VL5-VH5-VH4-CL、VL4-VL5-VH5-VH4-CH1-CL、VL4-VL5-VH5-VH4-CL-CH1、VH4-VH5-VL5、 -VL4-CH1、VH4-VH5-VL5-VL4-CL、VH4-VH5-VL5-VL4-CH1-CL、VH4-VH5-VL5-VL4-CL-CH1、VL4-L8-VL5-L9-VH5-L10-VH4-CH1、VL4-L8-VL5-L9-VH5-L10-VH4-CL、VL4-L8-VL5-L9-VH5-L10-VH4-CH1-CL、VL4-L8-VL5-L9-VH5-L10-VH4-CL-CH1、VH4-L8-VH5-L9-VL5-L10-VL4-CH1、VH4-L8-VH5-L9-VL5-L10-VL4-CL、VH4-L8-VH5-L9-VL5-L10-VL4-CH1-CL、VH4-L8-VH5-L9-VL5-L10-VL4-CL-CH1、VL4-VL5-VL6-VH6-VH5-VH4-CH1、VL4-VL5-VL6-VH6-VH5-VH4-CL、VL4-VL5-VL6-VH6-VH5-VH4-CH1-CL、VL4-VL5-VL6-VH6-VH5-VH4-CL-CH1、VH4-VH5-VH6-VL6-VL5-VL4-CH1、VH4-VH5-VH6-VL6-VL5-VL4-CL、VH4-VH5-VH6-VL6-VL5-VL4-CH1-CL、VH4-VH5-VH6-VL6-VL5-VL4-CL-CH1、VL4-VH5-VL6-VH6-VL5-VH4-CH1、VL4-VH5-VL6-VH6-VL5-VH4-CL、VL4-VH5-VL6-VH6-VL5-VH4-CH1-CL、VL4-VH5-VL6-VH6-VL5-VH4-CL-CH1、VH4-VL5-VH6-VL6-VH5-VL4-CH1、VH4-VL5-VH6-VL6-VH5-VL4-CL、VH4-VL5-VH6-VL6-VH5-VL4-CH1-CL、VH4-VL5-VH6-VL6-VH5-VL4-CL-CH1、VL4-VL5-VH6-VL6-VH5-VH4-CH1、VL4-VL5-VH6-VL6-VH5-VH4-CL、VL4-VL5-VH6-VL6-VH5-VH4-CH1-CL、VL4-VL5-VH6-VL6-VH5-VH4-CL-CH1、VH4-VH5-VL6-VH6-VL5-VL4-CH1、VH4-VH5-VL6-VH6-VL5-VL4-CL、VH4-VH5-VL6-VH6-VL5-VL4-CH1-CL、VH4-VH5-VL6-VH6-VL5-VL4-CL-CH1、VL4-VH5-VH6-VL6-VL5-VH4-CH1、VL4-VH5-VH6-VL6-VL5-VH4-CL、VL4-VH5-VH6-VL6-VL5-VH4-CH1-CL、VL4-VH5-VH6-VL6-VL5-VH4-CL-CH1、VH4-VL5-VL6-VH6-VH5-VL4-CH1、VH4-VL5-VL6-VH6-VH5-VL4-CL、VH4-VL5-VL6-VH6-VH5-VL4-CH1-CL、VH4-VL5-VL6-VH6-VH5-VL4-CL-CH1、VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-CH1、VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-CL、VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-CH1-CL、VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-CL-CH1、VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-CH1、VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-CL、VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-CH1-CL、VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-CL-CH1、VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-CH1、VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-CL、VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-CH1-CL、VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-CL-CH1、VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-CH1、VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-CL、VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-CH1-CL、VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-CL-CH1、VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-CH1、VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-CL、VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-CH1-CL、VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-CL-CH1、VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-CH1、VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-CL、VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-CH1-CL、VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-CL-CH1、VL4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VH4-CH1、VL4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VH4-CL、VL4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VH4-CH1-CL、VL4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VH4-CL-CH1、VH4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VL4-CH1、VH4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VL4-CL、VH4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VL4-CH1-CL、VH4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VL4-CL-CH1、VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-CL-CH1、VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-L13-CL、VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-L13-CH1-CL、VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-L13-CL-CH1、VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-L13-CH1、VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-L13-CL、VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-L13-CH1-CL、VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-L13-CL-CH1、VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-L13-CH1、VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-L13-CL、VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-L13-CH1-CL、VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-L13-CL-CH1、VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-L13-CH1、VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-L13-CL、VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-L13-CH1-CL、VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-L13-CL-CH1、VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-L13-CH1、VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-L13-CL、VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-L13-CH1-CL、VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-L13-CL-CH1、VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-L13-CH1、VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-L13-CL、VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-L13-CH1-CL, VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-L13-CL-CH1, VL4-L8-VH5- L9-VH6-L10-VL6-L11-VL5-L12-VH4-L13-CH1, VL4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VH4-L13-CL, VL4-L8-VH5-L9-VH6-L10-VL6-L11 -VL5-L12-VH4-L13-CH1-CL, VL4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VH4-L13-CH1, VH4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VL4-L 13-CH1, VH4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VL4-L13-CL, VH4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VL4-L13-CH1-CL, or VH4-L8 -VL5-L9-VL6-L10-VH6-L11-VH5-L12-VL4-L13-CL-CH1, where VL1 is a first immunoglobulin light chain variable region, VL2 is a second immunoglobulin light chain variable region, VL3 is a third immunoglobulin light chain variable region, VL4 is a fourth immunoglobulin light chain variable region, VL5 is a fifth immunoglobulin light chain variable region, VL6 is a sixth immunoglobulin light chain variable region, and VH1 is a first immunoglobulin heavy chain variable region. VH1 is a second immunoglobulin heavy chain variable region, VH2 is a second immunoglobulin heavy chain variable region, VH3 is a third immunoglobulin heavy chain variable region, VH4 is a fourth immunoglobulin heavy chain variable region, VH5 is a fifth immunoglobulin heavy chain variable region, VH6 is a sixth immunoglobulin heavy chain variable region, CH1 is heavy chain constant region 1, CL is a light chain constant region, and L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, and L13 are amino acid linkers.

[0025] The antigen-binding polypeptide complex containing the 1st polypeptide and the 2nd polypeptide is provided herein. Fc、VL1-VH2-VL3-VH3-VL2-VH1-CH1-Fc、VH1-VL2-VH3-VL3-VH2-VL1-CH1-Fc、VL1-VL2-VH3-VL3-VH2-VH1-CH1-Fc、VH1-VH2-VL3-VH3-VL2-VL1-CH1- Fc、VL1-VH2-VH3-VL3-VL2-VH1-CH1-Fc、VH1-VL2-VL3-VH3-VH2-VL1-CH1-Fc、VL1-VL2-VL3-VH3-VH2-VH1-CL-Fc、VH1-VH2-VH3-VL3-VL2-VL1-CL-Fc 、VL1-VH2-VL3-VH3-VL2-VH1-CL-Fc、VH1-VL2-VH3-VL3-VH2-VL1-CL-Fc、VL1-VL2-VH3-VL3-VH2-VH1-CL-Fc、VH1-VH2-VL3-VH3-VL2-VL1-CL-Fc、VL1- VH2-VH3-VL3-VL2-VH1-CL-Fc、VH1-VL2-VL3-VH3-VH2-VL1-CL-Fc、VL1-VL2-VL3-VH3-VH2-VH1-CH1-CL-Fc、VH1-VH2-VH3-VL3-VL2-VL1-CH1-CL-Fc、 VL1-VH2-VL3-VH3-VL2-VH1-CH1-CL-Fc、VH1-VL2-VH3-VL3-VH2-VL1-CH1-CL-Fc、VL1-VL2-VH3-VL3-VH2-VH1-CH1-CL-Fc、VH1-VH2-VL3-VH3-VL2-VL1 -CH1-CL-Fc、VL1-VH2-VH3-VL3-VL2-VH1-CH1-CL-Fc、VH1-VL2-VL3-VH3-VH2-VL1-CH1-CL-Fc、VL1-VL2-VL3-VH3-VH2-VH1-CL-CH1-Fc、VH1-VH2-VH3 -VL3-VL2-VL1-CL-CH1-Fc、VL1-VH2-VL3-VH3-VL2-VH1-CL-CH1-Fc、VH1-VL2-VH3-VL3-VH2-VL1-CL-CH1-Fc、VL1-VL2-VH3-VL3-VH2-VH1-CL-CH1-Fc、VH1-VH2-VL3-VH3-VL2-VL1-CL-CH1-Fc、VL1-VH2-VH3-VL3-VL2-VH1-CL-CH1-Fc、VH1-VL2-VL3-VH3-VH2-VL1-CL-CH1-Fc、VL1-L1-VL2-L2-VL3-L3 -VH3-L4-VH2-L5-VH1-CH1-Fc、VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CH1-Fc、VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CH1-Fc、VH1- L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CH1-Fc、VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CH1-Fc、VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5 -VL1-CH1-Fc、VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CH1-Fc、VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CH1-Fc、VL1-L1-VL2-L2-VL3- L3-VH3-L4-VH2-L5-VH1-CL-Fc、VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CL-Fc、VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CL-Fc、VH1-L 1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CL-Fc、VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CL-Fc、VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL 1-CL-Fc、VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CL-Fc、VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CL-Fc、VL1-L1-VL2-L2-VL3-L3-VH3 -L4-VH2-L5-VH1-CH1-CL-Fc、VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CH1-CL-Fc、VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CH1-CL-Fc、Structures represented by VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CH1-CL-Fc, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CH1-CL-Fc, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CH1-CL-Fc, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CH1-CL-Fc, VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CH1-CL-Fc, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CL-CH1-Fc, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CL-CH1-Fc, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CL-CH1-Fc, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CL-CH1-Fc, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CL-CH1-Fc, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CL-CH1-Fc, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CL-CH1-Fc, or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CL-CH1-Fc, and the second polypeptide is Fc, VL4-VH4-CH1-Fc, VL4-VHVL4-CH1-VH4-CL-Fc, VH4-CH1-VL4-CL-Fc, VL4-L6-CL-L7-VH4-L8-CH1-Fc, VL4-L6-CL-L7-VH4-L8-CH1-L9-Fc, VH4-L6-CL-L7-VL4-L8-CH1-Fc, VH 4-L6-CL-L7-VL4-L8-CH1-L9-Fc、VL4-L6-CH1-L7-VH4-L8-CL-Fc、VL4-L6-CH1-L7-VH4-L8-CL-L9-Fc、VH4-L6-CH1-L7-VL4-L8-CL-Fc、VH4-L6-CH1- L7-VL4-L8-CL-L9-Fc、VL4-VL5-VH5-VH4-CH1-Fc、VL4-VL5-VH5-VH4-CL- Fc、VL4-VL5-VH5-VH4-CH1-CL-Fc、VL4-VL5-VH5-VH4-CL-CH1-Fc、VH4-VH5 -VL5-VL4-CH1-Fc、VH4-VH5-VL5-VL4-CL-Fc、VH4-VH5-VL5-VL4-CH1-CL- Fc、VH4-VH5-VL5-VL4-CL-CH1-Fc、VL4-L6-VL5-L7-VH5-L8-VH4-CH1-Fc、V L4-L6-VL5-L7-VH5-L8-VH4-CL-Fc、VL4-L6-VL5-L7-VH5-L8-VH4-CH1-CL-Fc、VL4-L6-VL5-L7-VH5-L8-VH4-CL-CH1-Fc、VH4-L6-VH5-L7-VL5-L8-V L4-CH1-Fc, VH4-L6-VH5-L7-VL5-L8-VL4-CL-Fc, VH4-L6-VH5-L7-VL5-L8-VL4-CH1-CL-Fc, VH4-L6-VH5-L7-VL5-L8-VL4-CL-CH1-Fc, VL4-VL5-VL6- VH6-VH5-VH4-CH1-Fc、VL4-VL5-VL6-VH6-VH5-VH4-CL-Fc、VL4-VL5-VL6- VH6-VH5-VH4-CH1-CL-Fc、VL4-VL5-VL6-VH6-VH5-VH4-CL-CH1-Fc、VH4-VH 5-VH6-VL6-VL5-VL4-CH1-Fc、VH4-VH5-VH6-VL6-VL5-VL4-CL-Fc、VH4-VH 5-VH6-VL6-VL5-VL4-CH1-CL-Fc、VH4-VH5-VH6-VL6-VL5-VL4-CL-CH1-Fc、VL4-VH5-VL6-VH6-VL5-VH4-CH1-Fc、VL4-VH5-VL6-VH6-VL5-VH4-CL-Fc、VL4-VH5-VL6-VH6-VL5-VH4-CH1-CL-Fc、VL4-VH5-VL6-VH6-VL5-VH4-CL-CH1-Fc、VH4-VL5-VH6-VL6-VH5-VL4-CH1-Fc、VH4-VL5-VH6-VL6-VH5-VL4-CL-Fc、VH4-VL5-VH6-VL6-VH5-VL4-CH1-CL-Fc、VH4-VL5-VH6-VL6-VH5-VL4-CL-CH1-Fc、VL4-VL5-VH6-VL6-VH5-VH4-CH1-Fc、VL4-VL5-VH6-VL6-VH5-VH4-CL-Fc、VL4-VL5-VH6-VL6-VH5-VH4-CH1-CL-Fc、VL4-VL5-VH6-VL6-VH5-VH4-CL-CH1-Fc、VH4-VH5-VL6-VH6-VL5-VL4-CH1-Fc、VH4-VH5-VL6-VH6-VL5-VL4-CL-Fc、VH4-VH5-VL6-VH6-VL5-VL4-CH1-CL-Fc、VH4-VH5-VL6-VH6-VL5-VL4-CL-CH1-Fc、VL4-VH5-VH6-VL6-VL5-VH4-CH1-Fc、VL4-VH5-VH6-VL6-VL5-VH4-CL-Fc、VL4-VH5-VH6-VL6-VL5-VH4-CH1-CL-Fc、VL4-VH5-VH6-VL6-VL5-VH4-CL-CH1-Fc、VH4-VL5-VL6-VH6-VH5-VL4-CH1-Fc、VH4-VL5-VL6-VH6-VH5-VL4-CL-Fc、VH4-VL5-VL6-VH6-VH5-VL4-CH1-CL-Fc、VH4-VL5-VL6-VH6-VH5-VL4-CL-CH1-Fc、VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-CH1-Fc、VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-CL-Fc、VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-CH1-CL-Fc、VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-CL-CH1-Fc、VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-CH1-Fc, VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-CL-Fc, VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-CH1-CL-Fc, VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-CL-CH1-Fc, VL4-L6-VH5-L7-VL6-L 8-VH6-L9-VL5-L10-VH4-CH1-Fc、VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-CL-Fc、VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-CH1-CL-Fc、 VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-CL-CH1-Fc、VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-CH1-Fc、VH4-L6-VL5-L7-VH6-L8-VL6-L9 -VH5-L10-VL4-CL-Fc、VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-CH1-CL-Fc、VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-CL-CH1-Fc、VL4-L 6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4-CH1-Fc、VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4-CL-Fc、VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10- VH4-CH1-CL-Fc, VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4-CL-CH1-Fc, VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4-CH1-Fc, VH4-L6-VH5-L7 -VL6-L8-VH6-L9-VL5-L10-VL4-CL-Fc、VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4-CH1-CL-Fc、VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4-C L-CH1-Fc、VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4-CH1-Fc、VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4-CL-Fc、VL4-L6-VH5-L7-VH6-L8-V L6-L9-VL5-L10-VH4-CH1-CL-Fc、VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4-CL-CH1-Fc、VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-CH1-Fc、VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-CL-Fc、VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-CH1-CL-Fc、VH4-L6-VL5-L7-VL6-L8-VH6-L 9-VH5-L10-VL4-CL-CH1-Fc、VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-L11-CH1-Fc、VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-L11-CL-F c, VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-L11-CH1-CL-Fc, VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-L11-CL-CH1-Fc, VH4-L6-VH5-L7 -VH6-L8-VL6-L9-VL5-L10-VL4-L11-CH1-Fc、VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-L11-CL-Fc、VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-L11-CH1-CL-Fc、VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-L11-CL-CH1-Fc、VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-L11-CH1-F c, VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-L11-CL-Fc, VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-L11-CH1-CL-Fc, VL4-L6-VH5-L7-VL6 -L8-VH6-L9-VL5-L10-VH4-L11-CL-CH1-Fc、VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-L11-CH1-Fc、VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10 -VL4-L11-CL-Fc、VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-L11-CH1-CL-Fc、VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-L11-CL-CH1-Fc、VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4-L11-CH1-Fc, VL4-L6-VL5 -L7-VH6-L8-VL6-L9-VH5-L10-VH4-L11-CL-Fc, VL4-L6-VL5-L7-VH6-L8-V L6-L9-VH5-L10-VH4-L11-CH1-CL-Fc, VL4-L6-VL5-L7-VH6-L8-VL6-L9-V H5-L10-VH4-L11-CL-CH1-Fc, VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-V L4-L11-CH1-Fc, VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4-L11-CL- Fc, VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4-L11-CH1-CL-Fc, VH4-L 6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4-L11-CL-CH1-Fc, VL4-L6-VH5-L7 -VH6-L8-VL6-L9-VL5-L10-VH4-L11-CH1-Fc, VL4-L6-VH5-L7-VH6-L8-VL6 -L9-VL5-L10-VH4-L11-CL-Fc, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10 -VH4-L11-CH1-CL-Fc, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4-L11 -CL-CH1-Fc, VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-L11-CH1-Fc , VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-L11-CL-Fc, VH4-L6-VL5- L7-VL6-L8-VH6-L9-VH5-L10-VL4-L11-CH1-CL-Fc, or VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-L11-CL-CH1-Fc, wherein VL1 is a first immunoglobulin light chain variable region, VL2 is a second immunoglobulin light chain variable region, VL3 is a third immunoglobulin light chain variable region, VL4 is a fourth immunoglobulin light chain variable region, VL5 is a fifth immunoglobulin light chain variable region, and VL6 isand a sixth immunoglobulin light chain variable region, VH1 is a first immunoglobulin heavy chain variable region, VH2 is a second immunoglobulin heavy chain variable region, VH3 is a third immunoglobulin heavy chain variable region, VH4 is a fourth immunoglobulin heavy chain variable region, VH5 is a fifth immunoglobulin heavy chain variable region, and VH6 is a sixth immunoglobulin heavy chain variable region, Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge, CH1 is heavy chain constant region 1, CL is a light chain constant region, and L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, and L11 are amino acid linkers.

[0026] Provided herein are VL1-VL2-VL3-VH3-VH2-VH1-CH3-CH3, VH1-VH2-VH3-VL3-VL2-VL1-CH3-CH3, VL1-VH2-VL3-VH3-VL2-VH1-CH3-CH3, VH1-VL2-VH3-VL3-VH2-VL1-CH3-CH3, VL1-VL2-VH3-VL3-VH2-VH1-CH3-CH3, VH1-VH2-VL3-VH3-VL2-VL1-CH3-CH3, VL1-VH2-VH3-VL3-VL2-VH1-CH3-CH3, VH1-VL2-VL3-VH3-VH2-VL1-CH3-CH3, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CH3-CH3, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CH3-CH3, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CH3-CH3, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CH3-CH3, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CH3-CH3, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CH3-CH3, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CH3-CH3, VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CH3-CH3, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CH3-CH3, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CH3-CH3, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CH3-CH3, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CH3-CH3, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CH3-CH3, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CH3-CH3, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CH3-CH3,VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CH3-CH3, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6 -CH3-L7-CH3, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CH3-L7-CH3, VL1-L1-VH2-L2-VL3-L3-VH3-L4 -VL2-L5-VH1-L6-CH3-L7-CH3, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CH3-L7-CH3, VL1-L1-VL2-L 2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CH3-L7-CH3, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CH3-L7-CH 3, an antigen-binding polypeptide having a structure represented by VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CH3-L7-CH3, or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CH3-L7-CH3, wherein VL1 is a first immunoglobulin light chain variable region and VL2 is a second immunoglobulin light chain variable region. VL1 is a light chain variable region of a first immunoglobulin, VH2 is a second immunoglobulin heavy chain variable region, VH3 is a third immunoglobulin heavy chain variable region, CH3 is an immunoglobulin heavy chain constant region 3, and L1, L2, L3, L4, L5, L6, and L7 are amino acid linkers.

[0027] Provided herein are antigen-binding polypeptide complexes comprising a first polypeptide, a second polypeptide, and a third polypeptide, wherein the first polypeptide is selected from the group consisting of VL1-VL2-VL3-VH3-VH2-VH1, VH1-VH2-VH3-VL3-VL2-VL1, VL1-VH2-VL3-VH3-VL2-VH1, VH1-VL2-VH3-VL3-VH2-VL1, VL1-VL2-VH3-VL3-VH2-VL1, VL1-VL2-VH3-VL3-VH2-VH1, VL1-VL2-VH3-VL3-VH2-VH1, VL1-VL2-VH3-VL3-VH2-VH1, VL1-VH2-VL3-VH3-VL2-VL1, VL1-VH2-VH3-VL3-VL2-VH1, VL1-VH2-VL3-VH3-VL2-VH1, VL1-VH2-VL3-VH3-VL2-VH1, VL1-VH2-VH3-VL ... H1-VL2-VL3-VH3-VH2-VL1, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1 , VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1, VL1-L1-VH2-L2-VL3-L3-V H3-L4-VL2-L5-VH1, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1, VL1-L 1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1, VH1-L1-VH2-L2-VL3-L3-VH3-L4- the second polypeptide has a structure represented by VL4-VL5, VL4-L6-VL5, VL4-VL5-VL6, or VL4-L6-VL5-L7-VL6; and the third polypeptide has a structure represented by VH4-VH5, VH4-L6-VH5, VH4-VH5-VH6, or VH4-L6-VH5-L7-VH6. wherein VL1 is a first immunoglobulin light chain variable region, VL2 is a second immunoglobulin light chain variable region, VL3 is a third immunoglobulin light chain variable region, VL4 is a fourth immunoglobulin light chain variable region, VL5 is a fifth immunoglobulin light chain variable region, and VL6 is a sixth immunoglobulin light chain variable region; VH1 is a first immunoglobulin heavy chain variable region, VH2 is a second immunoglobulin heavy chain variable region, VH3 is a third immunoglobulin heavy chain variable region, and VH4 isVH5 is a fourth immunoglobulin heavy chain variable region, VH6 is a sixth immunoglobulin heavy chain variable region, and L1, L2, L3, L4, L5, L6, and L7 are amino acid linkers.

[0028] Provided herein is an antigen-binding polypeptide complex containing the 1st polypeptide, the 2nd polypeptide, and the 3rd polypeptide. 3-VL2-VL1-Fc、VL1-VH2-VL3-VH3-VL2-VH1-Fc、VH1-VL2-VH3-VL3-VH2-VL1-Fc、VL1-VL2-VH3-VL3-VH2-VH1-Fc、VH1-VH2-VL3-VH3-VL2-VL1-Fc Fc、VL1-VH2-VH3-VL3-VL2-VH1-Fc、VH1-VL2-VL3-VH3-VH2-VL1-Fc、VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-Fc、VL1-L1-VL2-L2-VL3-L 3-VH3-L4-VH2-L5-VH1-L6-Fc、VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-Fc、VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-Fc、VL1-L 1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-Fc、VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-Fc、VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH L1-Fc、VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-Fc、VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-Fc、VL1-L1-VL2-L2-VH3-L3-VL3- L4-VH2-L5-VH1-L6-Fc、VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-Fc、VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-Fc、VL1-L1-VH2- L2-VH3-L3-VL3-L4-VL2-L5-VH1-Fc、VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-Fc、VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-Fc、or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-Fc, and the second polypeptide is VL4-VL5, VL4-L7-VL5, VL4-CL, VL4-L7-CL, VL4-CH1, VL4-L7-CH1, VH4-VH5, VH4-L7-VH5, VH4-CL, VH4-L7-CL, VH4-CH1, VH4-L7-CH1, VL4-VL5-VL6, VL4-L7-VL5-L8-VL6, VL4-VL5-VL6-CL, VL4-L7-VL5-L8-VL6-CL, VL4-L7-VL5-L8-VL6-CL, VL4-L7-VL5-L8-VL6-L9-CL, VL4-VL5-VL6-CH1, VL4-L7-VL5-L8-VL6-CH1, VL4-L7-VL5-L8-VL6-L9-CH1, VH4-VH5-VH6, VH4-L7-VH5-L8-VH6, VH4-VH5 - Represented by VH6-CL, VH4-L7-VH5-L8-VH6-CL, VH4-L7-VH5-L8-VH6-L9-CL, VH4-VH5-VH6-CH1, VH4-L7-VH5-L8-VH6-CH1, or VH4-L7-VH5-L8-VH6-L9-CH1 and the third polypeptide has a structure represented by the formula (I) and (II), and the third polypeptide is VH4-VH5-Fc, VH4-L10-VH5-Fc, VH4-L10-VH5-L11-Fc, VH4-CH1-Fc, VH4-L10-CH1-Fc, VH4-L10-CH1-L11-Fc, VH4-CL-Fc, VH4-L10-CL-Fc, VH4-L10-CL-L11-Fc, VH4-VH5-Fc, VH4-L10-VH5-Fc, VH4-L10-VH5-L11-Fc, VH4-VH5-VH6-Fc, VH4-L10-VH5-L11-VH6-Fc, VH4-L10-VH5-L1 1-VH6-L12-Fc, VH4-VH5-VH6-CH1-Fc, VH4-L10-VH5-L11-VH6-CH1-Fc, VH4 -L10-VH5-L11-VH6-L12-CH1-Fc, VH4-L10-VH5-L11-VH6-L12-CH1-L13-Fc , VH4-VH5-VH6-CL-Fc, VH4-L10-VH5-L11-VH6-CL-Fc, VH4-L10-VH5-L11-V H6-L12-CL-Fc, VH4-L10-VH5-L11-VH6-L12-CL-L13-Fc, VL4-VL5-VL6-Fc,VL4-L10-VL5-L11-VL6-Fc, VL4-L10-VL5-L11-VL6-L12-Fc, VL4-VL5-VL6-CH1-Fc, VL4-L10-VL5-L11-VL6-CH1-Fc VL4-L10-VL5-L11-VL6-L12-CH1-Fc, VL4-L10-VL5-L11-VL6-L12-CH1-L13-Fc, VL4-VL5-VL6-CL-Fc , VL4-L10-VL5-L11-VL6-CL-Fc, VL4-L10-VL5-L11-VL6-L12-CL-Fc, or VL4-L10-VL5-L11-VL6-L12- CL-L13-Fc, where VL1 is a first immunoglobulin light chain variable region, VL2 is a second immunoglobulin light chain variable region, VL3 is a third immunoglobulin light chain variable region, VL4 is a fourth immunoglobulin light chain variable region, VL5 is a fifth immunoglobulin light chain variable region, and VL6 is a sixth immunoglobulin light chain variable region. VH1 is a first immunoglobulin heavy chain variable region, VH2 is a second immunoglobulin heavy chain variable region, VH3 is a third immunoglobulin heavy chain variable region, VH4 is a fourth immunoglobulin heavy chain variable region, VH5 is a fifth immunoglobulin heavy chain variable region, and VH6 is a sixth immunoglobulin heavy chain variable region, Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge, CH1 is heavy chain constant region 1, CL is a light chain constant region, and L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, and L13 are amino acid linkers.

[0029] Also provided herein are antigen-binding polypeptides or antigen-binding polypeptide complexes that specifically bind to viral peptides or HIV proteins.

[0030] Also provided herein are antibodies or antigen-binding fragments thereof comprising an antigen-binding polypeptide or an antigen-binding polypeptide described herein.

[0031] Also provided herein are polypeptides having at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 30-46, 94, and 96. Provided herein are polypeptides encoded by a polynucleotide having at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 47-63, 95, and 97.

[0032] Also provided herein are polynucleotides encoding the antigen-binding polypeptides or antigen-binding polypeptide complexes described herein. Provided herein are polynucleotides having at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 47-63, 95, and 97. Also provided herein are polynucleotides encoding polypeptides having at least 90% identity, at least 95% identity, or 100% identity to any one of SEQ ID NOs: 30-46, 94, and 96.

[0033] Also provided herein are vectors that include the polynucleotides described herein.

[0034] Also provided herein are host cells comprising the polynucleotides or vectors described herein.

[0035] Also provided herein is a chimeric antigen receptor (CAR) comprising an antigen-binding polypeptide or antigen-binding polypeptide complex described herein.

[0036] Also provided herein are immune cells comprising a CAR described herein.

[0037] Also provided herein is a pharmaceutical composition comprising (i) an antigen-binding polypeptide or antigen-binding polypeptide complex, an antibody or antigen-binding fragment thereof, a polypeptide, a polynucleotide, a vector, a host cell, a CAR, an immune cell, or a combination thereof, and (ii) a pharmaceutically acceptable carrier.

[0038] Also provided herein are kits comprising an antigen-binding polypeptide or antigen-binding polypeptide complex, an antibody or antigen-binding fragment thereof, a polypeptide, a polynucleotide, a vector, a host cell, a CAR, an immune cell, or a combination thereof.

[0039] Also provided herein are certain methods of using the antigen-binding polypeptides, antigen-binding polypeptide complexes, antibodies or antigen-binding fragments thereof, polypeptides, polynucleotides, vectors, host cells, CARs, or immune cells, or combinations thereof, described herein. [Brief explanation of the drawings]

[0040] Some aspects of the present invention are herein described, by way of example only, with reference to the accompanying drawings. Referring now specifically to the drawings in detail, it is emphasized that the details shown are by way of example and for purposes of illustrative discussion of aspects of the invention.

[0041] [Figure 1A]Figures 1A-1E show additional non-limiting examples of different configurations of single-chain trispecific antibody molecules. Figure 1A is a trispecific configuration without Fc. Figure 1B is a trispecific configuration with a single-chain Fc. Figure 1C is a trispecific configuration with a single-chain CH3. Figure 1D is a trispecific hexavalent configuration. Figure 1E is a trispecific configuration on one arm heterodimerizing with Fc. As used in Figures 1A-1E, vL1 is the first immunoglobulin light chain variable region, vL2 is the second immunoglobulin light chain variable region, vL3 is the third immunoglobulin light chain variable region, vH1 is the first immunoglobulin heavy chain variable region, vH2 is the second immunoglobulin heavy chain variable region, and vH3 is the third immunoglobulin heavy chain variable region. CH2 is immunoglobulin heavy chain constant region 2. CH3 is immunoglobulin heavy chain constant region 3. In Figure 1E, the circle symbol in the CH3 region is a knob-into-hole modification. [Figure 1B] Figures 1A-1E show additional non-limiting examples of different configurations of single-chain trispecific antibody molecules. Figure 1A is a trispecific configuration without Fc. Figure 1B is a trispecific configuration with a single-chain Fc. Figure 1C is a trispecific configuration with a single-chain CH3. Figure 1D is a trispecific hexavalent configuration. Figure 1E is a trispecific configuration on one arm heterodimerizing with Fc. As used in Figures 1A-1E, vL1 is the first immunoglobulin light chain variable region, vL2 is the second immunoglobulin light chain variable region, vL3 is the third immunoglobulin light chain variable region, vH1 is the first immunoglobulin heavy chain variable region, vH2 is the second immunoglobulin heavy chain variable region, and vH3 is the third immunoglobulin heavy chain variable region. CH2 is immunoglobulin heavy chain constant region 2. CH3 is immunoglobulin heavy chain constant region 3. In Figure 1E, the circle symbol in the CH3 region is a knob-into-hole modification. [Figure 1C]Figures 1A-1E show additional non-limiting examples of different configurations of single-chain trispecific antibody molecules. Figure 1A is a trispecific configuration without Fc. Figure 1B is a trispecific configuration with a single-chain Fc. Figure 1C is a trispecific configuration with a single-chain CH3. Figure 1D is a trispecific hexavalent configuration. Figure 1E is a trispecific configuration on one arm heterodimerizing with Fc. As used in Figures 1A-1E, vL1 is the first immunoglobulin light chain variable region, vL2 is the second immunoglobulin light chain variable region, vL3 is the third immunoglobulin light chain variable region, vH1 is the first immunoglobulin heavy chain variable region, vH2 is the second immunoglobulin heavy chain variable region, and vH3 is the third immunoglobulin heavy chain variable region. CH2 is immunoglobulin heavy chain constant region 2. CH3 is immunoglobulin heavy chain constant region 3. In Figure 1E, the circle symbol in the CH3 region is a knob-into-hole modification. [Figure 1D] Figures 1A-1E show additional non-limiting examples of different configurations of single-chain trispecific antibody molecules. Figure 1A is a trispecific configuration without Fc. Figure 1B is a trispecific configuration with a single-chain Fc. Figure 1C is a trispecific configuration with a single-chain CH3. Figure 1D is a trispecific hexavalent configuration. Figure 1E is a trispecific configuration on one arm heterodimerizing with Fc. As used in Figures 1A-1E, vL1 is the first immunoglobulin light chain variable region, vL2 is the second immunoglobulin light chain variable region, vL3 is the third immunoglobulin light chain variable region, vH1 is the first immunoglobulin heavy chain variable region, vH2 is the second immunoglobulin heavy chain variable region, and vH3 is the third immunoglobulin heavy chain variable region. CH2 is immunoglobulin heavy chain constant region 2. CH3 is immunoglobulin heavy chain constant region 3. In Figure 1E, the circle symbol in the CH3 region is a knob-into-hole modification. [Figure 1E]Figures 1A-1E show additional non-limiting examples of different configurations of single-chain trispecific antibody molecules. Figure 1A is a trispecific configuration without Fc. Figure 1B is a trispecific configuration with a single-chain Fc. Figure 1C is a trispecific configuration with a single-chain CH3. Figure 1D is a trispecific hexavalent configuration. Figure 1E is a trispecific configuration on one arm heterodimerizing with Fc. As used in Figures 1A-1E, vL1 is the first immunoglobulin light chain variable region, vL2 is the second immunoglobulin light chain variable region, vL3 is the third immunoglobulin light chain variable region, vH1 is the first immunoglobulin heavy chain variable region, vH2 is the second immunoglobulin heavy chain variable region, and vH3 is the third immunoglobulin heavy chain variable region. CH2 is immunoglobulin heavy chain constant region 2. CH3 is immunoglobulin heavy chain constant region 3. In Figure 1E, the circle symbol in the CH3 region is a knob-into-hole modification. [Figure 2A] ELISA results for the CD3-binding trispecific aCD28aCD3LHaCD38 LALAPAFc and the respective positive controls, aCD28aCD3 / aCD38Fab, or an isotype control (control IgG) are shown. The molecular structures are shown in FIG. 1A. [Figure 2B] ELISA results for the trispecific aCD28aCD3LHaCD38 LALAPAFc binding to CD28 and the respective positive controls, aCD28aCD3 / aCD38Fab, or an isotype control (control IgG). The molecular structures are shown in FIG. 1A. [Figure 2C] ELISA results for the trispecific aCD28aCD3LHaCD38 LALAPAFc binding to CD38 and the respective positive control, aCD28aCD3 / aCD38Fab, or an isotype control (control IgG) are shown. The molecular structures are shown in FIG. 1A. [Figure 3A]ELISA results for the trispecific aCD28aCD3LHaCD38 LALAPAFc, aCD3LHaCD28aCD38 LALAPAFc, aCD3LHaCD38aCD28 LALAPAFc, aCD28aCD3HLaCD38 LALAPAFc, or an isotype control (control IgG) that binds to CD3. The molecular structures are shown in FIG. 1E. [Figure 3B] ELISA results for the trispecific aCD28aCD3LHaCD38 LALAPAFc, aCD3LHaCD28aCD38 LALAPAFc, aCD3LHaCD38aCD28 LALAPAFc, aCD28aCD3HLaCD38 LALAPAFc, or an isotype control (control IgG) that binds to CD28. The molecular structures are shown in FIG. 1E. [Figure 3C] ELISA results for the trispecific aCD28aCD3LHaCD38 LALAPAFc, aCD3LHaCD28aCD38 LALAPAFc, aCD3LHaCD38aCD28 LALAPAFc, aCD28aCD3HLaCD38 LALAPAFc, or an isotype control (control IgG) that binds to CD38. The molecular structures are shown in FIG. 1E. [Figure 4A] Figure 4A shows NFκB (Figure 4A) and nuclear factor of activated T cells (NFAT) (Figure 4B) pathway activation by trispecific aCD28aCD3LHaCD38 LALAPAFc, aCD3LHaCD28aCD38 LALAPAFc, aCD3LHaCD38aCD28 LALAPAFc, aCD28aCD3HLaCD38 LALAPAFc, isotype control (control IgG), or anti-CD3 and anti-CD28 mAbs using NFκB or NFAT promoter-luciferase-expressing human Jurkat T cells. Molecular structures are shown in Figure 1E. [Figure 4B]Figure 4A shows NFκB (Figure 4A) and nuclear factor of activated T cells (NFAT) (Figure 4B) pathway activation by trispecific aCD28aCD3LHaCD38 LALAPAFc, aCD3LHaCD28aCD38 LALAPAFc, aCD3LHaCD38aCD28 LALAPAFc, aCD28aCD3HLaCD38 LALAPAFc, isotype control (control IgG), or anti-CD3 and anti-CD28 mAbs using NFκB or NFAT promoter-luciferase-expressing human Jurkat T cells. Molecular structures are shown in Figure 1E. [Figure 5] Non-limiting examples of different configurations of tetraspecific antibody molecules are shown. As used in Figure 5, vL1 is the first immunoglobulin light chain variable region, vL2 is the second immunoglobulin light chain variable region, vL3 is the third immunoglobulin light chain variable region, and vL4 is the fourth immunoglobulin light chain variable region. vH1 is the first immunoglobulin heavy chain variable region, vH2 is the second immunoglobulin heavy chain variable region, vH3 is the third immunoglobulin heavy chain variable region, and vH4 is the fourth immunoglobulin heavy chain variable region. CH2 is immunoglobulin heavy chain constant region 2. CH3 is immunoglobulin heavy chain constant region 3. The circle symbol in the CH3 region indicates a knob-into-hole modification. [Figure 6A] ELISA results for tetraspecific aCD28aCD3LHaCD38 / aCD19scFv, aCD28aCD3HLaCD38 / aCD19scFv, or an isotype control (control IgG) that binds to CD3 are shown. The molecular structures are shown in FIG. [Figure 6B] ELISA results for tetraspecific aCD28aCD3LHaCD38 / aCD19scFv, aCD28aCD3HLaCD38 / aCD19scFv, or an isotype control (control IgG) binding to CD28 are shown. The molecular structures are shown in FIG. [Figure 6C] ELISA results for tetraspecific aCD28aCD3LHaCD38 / aCD19scFv, aCD28aCD3HLaCD38 / aCD19scFv, or an isotype control (control IgG) binding to CD38 are shown. The molecular structures are shown in FIG. [Figure 6D] ELISA results for tetraspecific aCD28aCD3LHaCD38 / aCD19scFv, aCD28aCD3HLaCD38 / aCD19scFv, or an isotype control (control IgG) binding to CD19 are shown. The molecular structures are shown in FIG. [Figure 7] Non-limiting examples of different configurations of pentaspecific antibody molecules are shown. As used in Figure 7, vL1 is the first immunoglobulin light chain variable region, vL2 is the second immunoglobulin light chain variable region, vL3 is the third immunoglobulin light chain variable region, vL4 is the fourth immunoglobulin light chain variable region, and vL5 is the fifth immunoglobulin light chain variable region. vH1 is the first immunoglobulin heavy chain variable region, vH2 is the second immunoglobulin heavy chain variable region, vH3 is the third immunoglobulin heavy chain variable region, vH4 is the fourth immunoglobulin heavy chain variable region, and vH5 is the fifth immunoglobulin heavy chain variable region. CH2 is immunoglobulin heavy chain constant region 2. CH3 is immunoglobulin heavy chain constant region 3. The circle symbol in the CH3 region indicates a knob-into-hole modification. [Figure 8A] ELISA results for tetraspecific aCD28aCD3LHaCD38 / aCD19aCD20, aCD28aCD3LHaCD38 / aCD20aCD19, aCD28aCD3HLaCD38 / aCD19aCD20, aCD28aCD3HLaCD38 / aCD20aCD19, or an isotype control (control IgG) that binds to CD3. Molecular structures are shown in FIG. [Figure 8B] ELISA results for tetraspecific aCD28aCD3LHaCD38 / aCD19aCD20, aCD28aCD3LHaCD38 / aCD20aCD19, aCD28aCD3HLaCD38 / aCD19aCD20, aCD28aCD3HLaCD38 / aCD20aCD19, or an isotype control (control IgG) that binds to CD28 are shown. Molecular structures are shown in FIG. [Figure 8C]ELISA results for tetraspecific aCD28aCD3LHaCD38 / aCD19aCD20, aCD28aCD3LHaCD38 / aCD20aCD19, aCD28aCD3HLaCD38 / aCD19aCD20, aCD28aCD3HLaCD38 / aCD20aCD19, or an isotype control (control IgG) that binds to CD38 are shown. The molecular structures are shown in FIG. [Figure 8D] ELISA results for tetraspecific aCD28aCD3LHaCD38 / aCD19aCD20, aCD28aCD3LHaCD38 / aCD20aCD19, aCD28aCD3HLaCD38 / aCD19aCD20, aCD28aCD3HLaCD38 / aCD20aCD19, or an isotype control (control IgG) that binds to CD19 are shown. Molecular structures are shown in FIG. [Figure 9] Non-limiting examples of different configurations of hexaspecific antibody molecules are shown. As used in Figure 9, vL1 is the first immunoglobulin light chain variable region, vL2 is the second immunoglobulin light chain variable region, vL3 is the third immunoglobulin light chain variable region, vL4 is the fourth immunoglobulin light chain variable region, vL5 is the fifth immunoglobulin light chain variable region, and vL6 is the sixth immunoglobulin light chain variable region. vH1 is the first immunoglobulin heavy chain variable region, vH2 is the second immunoglobulin heavy chain variable region, vH3 is the third immunoglobulin heavy chain variable region, vH4 is the fourth immunoglobulin heavy chain variable region, vH5 is the fifth immunoglobulin heavy chain variable region, and vH6 is the sixth immunoglobulin heavy chain variable region. CH2 is immunoglobulin heavy chain constant region 2. CH3 is immunoglobulin heavy chain constant region 3. The circle symbol in the CH3 region indicates a knob-into-hole modification. [Figure 10A] Biolayer interferometry (BLI) of the hexaspecific aCD3aCD28LHaCD38 / aCD33aCD123LHaBCMA antibody binding to CD3 at 80 nM. The molecular structure is shown in Figure 9. [Figure 10B]Biolayer interferometry (BLI) of the hexaspecific aCD3aCD28LHaCD38 / aCD33aCD123LHaBCMA antibody at 80 nM, binding to CD28. The molecular structure is shown in FIG. [Figure 10C] Biolayer interferometry (BLI) of the hexaspecific aCD3aCD28LHaCD38 / aCD33aCD123LHaBCMA antibody at 80 nM binding to CD38. The molecular structure is shown in FIG. [Figure 10D] Biolayer interferometry (BLI) of the hexaspecific aCD3aCD28LHaCD38 / aCD33aCD123LHaBCMA antibody binding to CD33 at 80 nM. The molecular structure is shown in FIG. [Figure 10E] Biolayer interferometry (BLI) of the hexaspecific aCD3aCD28LHaCD38 / aCD33aCD123LHaBCMA antibody binding to CD123 at 80 nM. The molecular structure is shown in FIG. [Figure 10F] Biolayer interferometry (BLI) of the hexaspecific aCD3aCD28LHaCD38 / aCD33aCD123LHaBCMA antibody binding to BCMA at 80 nM. The molecular structure is shown in Figure 9. [Figure 11A] Biolayer interferometry (BLI) of the hexaspecific aCD3aCD28LHaCD38 / aCD123aBCMALHaCD33 antibody binding to CD3 at 40 nM. The molecular structure is shown in FIG. [Figure 11B] Biolayer interferometry (BLI) of the hexaspecific aCD3aCD28LHaCD38 / aCD123aBCMALHaCD33 antibody at 40 nM, binding to CD28. The molecular structure is shown in FIG. [Figure 11C] Biolayer interferometry (BLI) of the hexaspecific aCD3aCD28LHaCD38 / aCD123aBCMALHaCD33 antibody binding to CD38 at 40 nM. The molecular structure is shown in FIG. [Figure 11D]Biolayer interferometry (BLI) of the hexaspecific aCD3aCD28LHaCD38 / aCD123aBCMALHaCD33 antibody binding to CD33 at 40 nM. The molecular structure is shown in FIG. [Figure 11E] Biolayer interferometry (BLI) of the hexaspecific aCD3aCD28LHaCD38 / aCD123aBCMALHaCD33 antibody binding to CD123 at 40 nM. The molecular structure is shown in FIG. [Figure 11F] Biolayer interferometry (BLI) of the hexaspecific aCD3aCD28LHaCD38 / aCD123aBCMALHaCD33 antibody binding to BCMA at 40 nM. The molecular structure is shown in Figure 9. [Figure 12A] Figures 12A-12F show exemplary bispecific molecule configurations from the N-terminus to the C-terminus of the single-chain antigen-binding polypeptide(s). Figures 12A, 12D, and 12F are bispecific molecules without an Fc region. Figures 12B and 12F are bispecific tetravalent molecules with an Fc region. Figures 12C, 12E, and 12F are bispecific molecules with an Fc region. As used in Figures 12A-12F, VL1 refers to the first immunoglobulin light chain variable region, VL2 refers to the second immunoglobulin light chain variable region, VH1 refers to the first immunoglobulin heavy chain variable region, and VH2 refers to the second immunoglobulin heavy chain variable region. In Figures 12B, 12C, and 12F, CH2 refers to immunoglobulin heavy chain constant region 2, and CH3 refers to immunoglobulin heavy chain constant region 3. In Figures 12A and 12F, l1, l2, and l3 refer to amino acid linkers. In Figure 12D, L1, L2, and L3 refer to amino acid linkers. In Figures 12C and 12F, the circle symbol refers to a knob-into-hole modification. [Figure 12B]Figures 12A-12F show exemplary bispecific molecule configurations from the N-terminus to the C-terminus of the single-chain antigen-binding polypeptide(s). Figures 12A, 12D, and 12F are bispecific molecules without an Fc region. Figures 12B and 12F are bispecific tetravalent molecules with an Fc region. Figures 12C, 12E, and 12F are bispecific molecules with an Fc region. As used in Figures 12A-12F, VL1 refers to the first immunoglobulin light chain variable region, VL2 refers to the second immunoglobulin light chain variable region, VH1 refers to the first immunoglobulin heavy chain variable region, and VH2 refers to the second immunoglobulin heavy chain variable region. In Figures 12B, 12C, and 12F, CH2 refers to immunoglobulin heavy chain constant region 2, and CH3 refers to immunoglobulin heavy chain constant region 3. In Figures 12A and 12F, l1, l2, and l3 refer to amino acid linkers. In Figure 12D, L1, L2, and L3 refer to amino acid linkers. In Figures 12C and 12F, the circle symbol refers to a knob-into-hole modification. [Figure 12C] Figures 12A-12F show exemplary bispecific molecule configurations from the N-terminus to the C-terminus of the single-chain antigen-binding polypeptide(s). Figures 12A, 12D, and 12F are bispecific molecules without an Fc region. Figures 12B and 12F are bispecific tetravalent molecules with an Fc region. Figures 12C, 12E, and 12F are bispecific molecules with an Fc region. As used in Figures 12A-12F, VL1 refers to the first immunoglobulin light chain variable region, VL2 refers to the second immunoglobulin light chain variable region, VH1 refers to the first immunoglobulin heavy chain variable region, and VH2 refers to the second immunoglobulin heavy chain variable region. In Figures 12B, 12C, and 12F, CH2 refers to immunoglobulin heavy chain constant region 2, and CH3 refers to immunoglobulin heavy chain constant region 3. In Figures 12A and 12F, l1, l2, and l3 refer to amino acid linkers. In Figure 12D, L1, L2, and L3 refer to amino acid linkers. In Figures 12C and 12F, the circle symbol refers to a knob-into-hole modification. [Figure 12D]Figures 12A-12F show exemplary bispecific molecule configurations from the N-terminus to the C-terminus of the single-chain antigen-binding polypeptide(s). Figures 12A, 12D, and 12F are bispecific molecules without an Fc region. Figures 12B and 12F are bispecific tetravalent molecules with an Fc region. Figures 12C, 12E, and 12F are bispecific molecules with an Fc region. As used in Figures 12A-12F, VL1 refers to the first immunoglobulin light chain variable region, VL2 refers to the second immunoglobulin light chain variable region, VH1 refers to the first immunoglobulin heavy chain variable region, and VH2 refers to the second immunoglobulin heavy chain variable region. In Figures 12B, 12C, and 12F, CH2 refers to immunoglobulin heavy chain constant region 2, and CH3 refers to immunoglobulin heavy chain constant region 3. In Figures 12A and 12F, l1, l2, and l3 refer to amino acid linkers. In Figure 12D, L1, L2, and L3 refer to amino acid linkers. In Figures 12C and 12F, the circle symbol refers to a knob-into-hole modification. [Figure 12E] Figures 12A-12F show exemplary bispecific molecule configurations from the N-terminus to the C-terminus of the single-chain antigen-binding polypeptide(s). Figures 12A, 12D, and 12F are bispecific molecules without an Fc region. Figures 12B and 12F are bispecific tetravalent molecules with an Fc region. Figures 12C, 12E, and 12F are bispecific molecules with an Fc region. As used in Figures 12A-12F, VL1 refers to the first immunoglobulin light chain variable region, VL2 refers to the second immunoglobulin light chain variable region, VH1 refers to the first immunoglobulin heavy chain variable region, and VH2 refers to the second immunoglobulin heavy chain variable region. In Figures 12B, 12C, and 12F, CH2 refers to immunoglobulin heavy chain constant region 2, and CH3 refers to immunoglobulin heavy chain constant region 3. In Figures 12A and 12F, l1, l2, and l3 refer to amino acid linkers. In Figure 12D, L1, L2, and L3 refer to amino acid linkers. In Figures 12C and 12F, the circle symbol refers to a knob-into-hole modification. [Figure 12F]Figures 12A-12F show exemplary bispecific molecule configurations from the N-terminus to the C-terminus of the single-chain antigen-binding polypeptide(s). Figures 12A, 12D, and 12F are bispecific molecules without an Fc region. Figures 12B and 12F are bispecific tetravalent molecules with an Fc region. Figures 12C, 12E, and 12F are bispecific molecules with an Fc region. As used in Figures 12A-12F, VL1 refers to the first immunoglobulin light chain variable region, VL2 refers to the second immunoglobulin light chain variable region, VH1 refers to the first immunoglobulin heavy chain variable region, and VH2 refers to the second immunoglobulin heavy chain variable region. In Figures 12B, 12C, and 12F, CH2 refers to immunoglobulin heavy chain constant region 2, and CH3 refers to immunoglobulin heavy chain constant region 3. In Figures 12A and 12F, l1, l2, and l3 refer to amino acid linkers. In Figure 12D, L1, L2, and L3 refer to amino acid linkers. In Figures 12C and 12F, the circle symbol refers to a knob-into-hole modification. [Figure 13] FIG. 12B shows the SDS-PAGE results of nickel-NTA (Ni-NTA) purified bispecific molecules with histidine tags shown in FIG. 12A. [Figure 14] ELISA results for the bispecific molecule aCD19aCD38-His that binds to CD19 (A) and CD38 (B) or an isotype control (control IgG) are shown. [Figure 15] FIG. 12B shows the SDS-PAGE results of Protein A purified bispecific tetravalent molecules with LALAPA Fc. [Figure 16A] ELISA results for bispecific tetravalent aCD28aCD3LALAPAFc, aCD3aCD28LALAPAFc, or an isotype control (control IgG) that binds to CD3 (A) and CD28 (B) are shown. The molecular structures are shown in FIG. [Figure 16B] ELISA results for bispecific tetravalent aCD28aCD3LALAPAFc, aCD3aCD28LALAPAFc, or an isotype control (control IgG) that binds to CD3 (A) and CD28 (B) are shown. The molecular structures are shown in FIG. [Figure 17] 1 shows nuclear factor of activated T cells (NFAT) pathway activation by bispecific tetravalent aCD28aCD3L1LALAPAFc or aCD3aCD28L1LALAPAFc, or anti-CD3 and anti-CD28 mAbs using NFAT promoter-luciferase expressing human Jurkat T cells. [Figure 18] ELISA results for bispecific aCD28aCD3LALAPAFc or aCD3aCD28LALAPAFc binding to CD3 (A) and CD28 (B), or an isotype control (control IgG), are shown. The molecular structures are shown in FIG. 12C. [Figure 19] The configuration of an exemplary tetraspecific molecule is shown. VL1 refers to the first immunoglobulin light chain variable region. VL2 refers to the second immunoglobulin light chain variable region. VL3 refers to the third immunoglobulin light chain variable region. VL4 refers to the fourth immunoglobulin light chain variable region. VH1 refers to the first immunoglobulin heavy chain variable region. VH2 refers to the second immunoglobulin heavy chain variable region. VH3 refers to the third immunoglobulin heavy chain variable region. VH4 refers to the fourth immunoglobulin heavy chain variable region. CH1 refers to immunoglobulin heavy chain constant region 1. CH2 refers to immunoglobulin heavy chain constant region 2. CH3 refers to immunoglobulin heavy chain constant region 3. CL refers to an immunoglobulin light chain constant region. The circle symbols A through C refer to knob-into-hole modifications. [Figure 20] ELISA results for tetraspecific aCD28aCD3CD19CD38LALAPAFc, aCD3aCD28CD19CD38LALAPAFc, aCD28aCD3CD19CD38LALAPAFc, or aCD28aCD3CD38CD19LALAPAFc, which bind to CD3 (A), CD28 (B), CD19 (C), and CD38 (D), or an isotype control (control IgG) are shown. The molecular structures are shown in Figure 19A. [Figure 21]NFκB pathway activation by tetraspecific aCD28aCD3 / aCD19CD38L1LALAPAFc or aCD3aCD28 / CD19CD38L1LALAPAFc, or anti-CD3 mAb, using NFκB promoter-luciferase expressing human Jurkat T cells. [Figure 22] Activation of CD4+ (A) or CD8+ (B) T cells from three different donors with the tetraspecific molecules aCD28aCD3 / aCD19CD38L1LALAPAFc or aCD3aCD28 / CD19CD38L1LALAPAFc, or with anti-CD3 mAb (CD69+) is shown. [Figure 23] This shows that both the orientation and the linker can affect the expression of the tetraspecific molecule. [Figure 24] 24 shows the ELISA results of tetraspecific aCD28aCD3CD19CD38LALAPAFc with different linker lengths as shown in FIG. 23, or an isotype control (control IgG), binding to CD3 (A), CD28 (B), CD19 (C), and CD38 (D). [Figure 25-1] Figure 25A shows ELISA results for tetraspecific aCD28aCD3CH1 / CD19CD38CLLALAPAFc with different linker lengths as shown in Figure 19B binding to CD3, or an isotype control (control IgG), and Figure 25B shows ELISA results for tetraspecific aCD28aCD3CH1 / CD19CD38CLLALAPAFc with different linker lengths as shown in Figure 19B binding to CD28, or an isotype control (control IgG). [Figure 25-2] Figure 25C shows ELISA results for tetraspecific aCD28aCD3CH1 / CD19CD38CLLALAPAFc with different linker lengths as shown in Figure 19B, or an isotype control (control IgG), binding to CD38. Figure 25D shows ELISA results for tetraspecific aCD28aCD3CH1 / CD19CD38CLLALAPAFc with different linker lengths as shown in Figure 19B, or an isotype control (control IgG), binding to CD19. [Figure 26A]ELISA results for tetraspecific aCD28aCD3CD38CD19LALAPAFc, aCD28aCD3CD38CD19LALAPAFc, aCD28aCD3CD38CD19LALAPAFc, or aCD3aCD28CD19CD38LALAPAFc binding to CD3, or an isotype control (control IgG), are shown. The molecular structures are shown in FIG. 19C. [Figure 26B] ELISA results for tetraspecific aCD28aCD3CD38CD19LALAPAFc, aCD28aCD3CD38CD19LALAPAFc, aCD28aCD3CD38CD19LALAPAFc, or aCD3aCD28CD19CD38LALAPAFc binding to CD28, or an isotype control (control IgG), are shown. The molecular structures are shown in FIG. 19C. [Figure 26C] ELISA results for tetraspecific aCD28aCD3CD38CD19LALAPAFc, aCD28aCD3CD38CD19LALAPAFc, aCD28aCD3CD38CD19LALAPAFc, or aCD3aCD28CD19CD38LALAPAFc binding to CD38, or an isotype control (control IgG), are shown. The molecular structures are shown in FIG. 19C. [Figure 26D] ELISA results for tetraspecific aCD28aCD3CD38CD19LALAPAFc, aCD28aCD3CD38CD19LALAPAFc, aCD28aCD3CD38CD19LALAPAFc, or aCD3aCD28CD19CD38LALAPAFc binding to CD19, or an isotype control (control IgG), are shown. The molecular structures are shown in FIG. 19C. [Figure 26E] ELISA results for tetraspecific aCD28aCD3L1 / aCD38aCD19L1_HHLL, aCD28aCD3L1 / aCD19aCD38L1_HHLL, aCD3aCD28L1 / aCD38aCD19L1_HHLL, aCD3aCD28L1 / aCD19aCD38L1_HHLL, or an isotype control (control IgG) binding to CD3 are shown. [Figure 26F]ELISA results for tetraspecific aCD28aCD3L1 / aCD38aCD19L1_HHLL, aCD28aCD3L1 / aCD19aCD38L1_HHLL, aCD3aCD28L1 / aCD38aCD19L1_HHLL, aCD3aCD28L1 / aCD19aCD38L1_HHLL, or an isotype control (control IgG) binding to CD28 are shown. [Figure 26G] ELISA results for tetraspecific aCD28aCD3L1 / aCD38aCD19L1_HHLL, aCD28aCD3L1 / aCD19aCD38L1_HHLL, aCD3aCD28L1 / aCD38aCD19L1_HHLL, aCD3aCD28L1 / aCD19aCD38L1_HHLL, or an isotype control (control IgG) binding to CD38 are shown. [Figure 26H] ELISA results for tetraspecific aCD28aCD3L1 / aCD38aCD19L1_HHLL, aCD28aCD3L1 / aCD19aCD38L1_HHLL, aCD3aCD28L1 / aCD38aCD19L1_HHLL, aCD3aCD28L1 / aCD19aCD38L1_HHLL, or an isotype control (control IgG) binding to CD19 are shown. [Figure 27] Figures 27A-27D show the configuration of exemplary bispecific molecules of the invention. VL1 refers to a first immunoglobulin light chain variable region. VL2 refers to a second immunoglobulin light chain variable region. VL3 refers to a third immunoglobulin light chain variable region. VL4 refers to a fourth immunoglobulin light chain variable region. VH1 refers to a first immunoglobulin heavy chain variable region. VH2 refers to a second immunoglobulin heavy chain variable region. VH3 refers to a third immunoglobulin heavy chain variable region. VH4 refers to a fourth immunoglobulin heavy chain variable region. CH3 refers to immunoglobulin heavy chain constant region 3. [Figure 28A] 1 shows an exemplary configuration of a triabody molecule: bispecific arms paired with scFv-Fc. [Figure 28B] 1 shows an exemplary configuration of a triabody molecule: bispecific arms paired with Fab-Fc. [Figure 28C]1 shows an exemplary configuration of a triabody molecule: a bispecific arm paired with a single-chain Fab (scFab). [Figure 28D] 1 shows an exemplary configuration of a triabody molecule: a bispecific arm paired with a scFv single chain CL-CH1-Fc. [Figure 28E] It is a bispecific arm fused to CH1 and paired with scFv-CL-Fc. [Figure 29A] 28A-28D show ELISA results for the trispecific aCD28aCD3 / aCD38scFv, aCD28aCD3 / aCD38Fab, aCD28aCD3 / aCD38scFab, aCD28aCD3 / aCD38CLCH1, or an isotype control (control IgG) that binds to CD3. Molecular structures are shown in Figures 28A-28D. [Figure 29B] ELISA results for the trispecific aCD28aCD3 / aCD38scFv, aCD28aCD3 / aCD38Fab, aCD28aCD3 / aCD38scFab, aCD28aCD3 / aCD38CLCH1, or an isotype control (control IgG) that binds to CD28. Molecular structures are shown in Figures 28A-28D. [Figure 29C] ELISA results for the trispecific aCD28aCD3 / aCD38scFv, aCD28aCD3 / aCD38Fab, aCD28aCD3 / aCD38scFab, aCD28aCD3 / aCD38CLCH1, or an isotype control (control IgG) binding to CD38 are shown in Figures 28A-28D. [Figure 30] Activation (CD69+) of CD2+ T cells from three different donors with trispecific antibodies aCD28aCD3L1 / aCD38scFv, aCD3aCD28 / aCD38scFv, aCD28aCD3 / aCD38scFab, aCD3aCD28 / aCD38scFab, PMA / IO positive or negative isotype (control IgG) control is shown. [Figure 31-1]In vitro cytolysis of lymphoma tumor cells Z-138 by T cells mediated by trispecific antibodies aCD28aCD3L1 / aCD38scFv, aCD3aCD28 / aCD38scFv, aCD28aCD3 / aCD38scFab, aCD3aCD28 / aCD38scFab, PMA / IO, or isotype (control IgG) control from three different donors (A-B, respectively). [Figure 31-2] In vitro cytolysis of lymphoma tumor cells Z-138 by T cells mediated by trispecific antibodies aCD28aCD3L1 / aCD38scFv, aCD3aCD28 / aCD38scFv, aCD28aCD3 / aCD38scFab, aCD3aCD28 / aCD38scFab, PMA / IO, or an isotype (control IgG) control from three different donors (C). [Figure 32A] ELISA results for trispecific aCD28aCD3CL1CH1 / aCD38scFvCL, aCD28aCD3CL1CH1 / aCD19scFvCL, or an isotype control (control IgG) that binds to CD3 are shown in Figure 28E. [Figure 32B] ELISA results for trispecific aCD28aCD3CL1CH1 / aCD38scFvCL, aCD28aCD3CL1CH1 / aCD19scFvCL, or an isotype control (control IgG) binding to CD28 are shown. The molecular structures are shown in Figure 28E. [Figure 32C] ELISA results for trispecific aCD28aCD3CL1CH1 / aCD38scFvCL, aCD28aCD3CL1CH1 / aCD19scFvCL, or an isotype control (control IgG) binding to CD19 are shown. The molecular structures are shown in Figure 28E. [Figure 32D] ELISA results for trispecific aCD28aCD3CL1CH1 / aCD38scFvCL, aCD28aCD3CL1CH1 / aCD19scFvCL, or an isotype control (control IgG) binding to CD38 are shown. The molecular structures are shown in Figure 28E. [Figure 33] 10 shows additional non-limiting examples of different configurations of tetraspecific antibody molecules. [Figure 34] 1 shows an exemplary configuration of a masked tetraspecific antibody. The antibody variable domains (Fv) are shown as heavy / light chain pairs, with Fv1 through Fv3 targeting tumor-associated antigens (TAAs) or immune co-stimulatory receptors, and a fourth Fv targeting CD3 (αCD3 or αCD3). In some embodiments, the linker between Fv3 and αCD3 contains one or more protease recognition sites. [Figure 35] 1 shows SDS-PAGE results of in vitro cleavage of the exemplary masked tetraspecific molecules shown. The molecules were treated with either MTP or MMP9 protease as indicated. [Figure 36] Figures 36A-D show ELISA binding results for the exemplary masked tetraspecific molecules shown in Figure 35 with or without protease treatment, or a negative isotype (control IgG1). The molecules, cleaved or uncleaved by the indicated MTP or MMP9, were tested for binding affinity to Trop2 and cMet. [Figure 37] Figures 37A-B show ELISA binding results for the exemplary masked tetraspecific molecules shown in Figure 35 with or without protease treatment, or a negative isotype (control IgG1). The molecules, cleaved or uncleaved by the indicated MTP or MMP9, were tested for binding affinity to CD28. [Figure 38A] Figure 35 shows ELISA binding results for the exemplary masked tetraspecific molecules shown in Figure 35 with or without protease treatment, or a negative isotype (control IgG1). The molecules, cleaved or uncleaved by the indicated MTP or MMP9, were tested for binding affinity to CD3. [Figure 38B]Figure 35 shows ELISA binding results for the exemplary masked tetraspecific molecules shown in Figure 35 with or without protease treatment, or a negative isotype (control IgG1). The molecules, cleaved or uncleaved by the indicated MTP or MMP9, were tested for binding affinity to CD3. [Figure 38C] Figure 35 shows ELISA binding results for the exemplary masked tetraspecific molecules shown in Figure 35 with or without protease treatment, or a negative isotype (control IgG1). The molecules, cleaved or uncleaved by the indicated MTP or MMP9, were tested for binding affinity to CD3. [Figure 38D] Figure 35 shows ELISA binding results for the exemplary masked tetraspecific molecules shown in Figure 35 with or without protease treatment, or a negative isotype (control IgG1). The molecules, cleaved or uncleaved by the indicated MTP or MMP9, were tested for binding affinity to CD3. [Figure 38E] Figure 35 shows ELISA binding results for the exemplary masked tetraspecific molecules shown in Figure 35 with or without protease treatment, or a negative isotype (control IgG1). The molecules, cleaved or uncleaved by the indicated MTP or MMP9, were tested for binding affinity to CD3. [Figure 38F] Figure 35 shows ELISA binding results for the exemplary masked tetraspecific molecules shown in Figure 35 with or without protease treatment, or a negative isotype (control IgG1). The molecules, cleaved or uncleaved by the indicated MTP or MMP9, were tested for binding affinity to CD3. [Figure 39] Figures 39A-B show cytolysis of HCC1954 tumor cells by PBMCs (E:T:10:1) mediated by the exemplary masked tetraspecific molecule shown in Figure 13 or a negative isotype (control IgG1) from PBMCs of two donors (KP63250 and KP63251). [Figure 40] ELISA binding results of the indicated exemplary unmasked tetraspecific molecules, or a negative isotype (hIgG1LALPA) control, against their respective targets: hTrop2, hcMet, hCD28, and hCD3. [Figure 41] AB show CD69+ activation of CD2+ T cells from PBMCs of two different donors by an exemplary unmasked tetraspecific molecule or a negative isotype (IgG1LALPA) control. [Figure 42] 10 shows additional non-limiting examples of tetraspecific antibody molecules. [Figure 43A] Figure 43A shows a further non-limiting example of a tetravalent bispecific antibody construct called MX846. MX846 was analyzed for binding to CD3 by biolayer interferometry (BLI) (Figure 43B) and CD20 by flow cytometry (Figure 43C). [Figure 43B] Figure 43A shows a further non-limiting example of a tetravalent bispecific antibody construct called MX846. MX846 was analyzed for binding to CD3 by biolayer interferometry (BLI) (Figure 43B) and CD20 by flow cytometry (Figure 43C). [Figure 43C] Figure 43A shows a further non-limiting example of a tetravalent bispecific antibody construct called MX846. MX846 was analyzed for binding to CD3 by biolayer interferometry (BLI) (Figure 43B) and CD20 by flow cytometry (Figure 43C). [Figure 44A] Figure 44A shows a further non-limiting example of a tetravalent trispecific antibody construct called MX855. MX855 was analyzed for binding to CD3 and CD28 by biolayer interferometry (BLI) (Figure 44B), and for binding to CD20 by flow cytometry (Figure 44C). [Figure 44B]Figure 44A shows a further non-limiting example of a tetravalent trispecific antibody construct called MX855. MX855 was analyzed for binding to CD3 and CD28 by biolayer interferometry (BLI) (Figure 44B), and for binding to CD20 by flow cytometry (Figure 44C). [Figure 44C] Figure 44A shows a further non-limiting example of a tetravalent trispecific antibody construct called MX855. MX855 was analyzed for binding to CD3 and CD28 by biolayer interferometry (BLI) (Figure 44B), and for binding to CD20 by flow cytometry (Figure 44C). [Figure 45A] Figure 45A shows a further non-limiting example of a tetraspecific antibody construct called MX851. MX851 was analyzed for binding to CD3, CD28, and BCMA by biolayer interferometry (BLI) (Figure 45B), and for binding to CD20 by flow cytometry (Figure 45C). [Figure 45B] Figure 45A shows a further non-limiting example of a tetraspecific antibody construct called MX851. MX851 was analyzed for binding to CD3, CD28, and BCMA by biolayer interferometry (BLI) (Figure 45B), and for binding to CD20 by flow cytometry (Figure 45C). [Figure 45C] Figure 45A shows a further non-limiting example of a tetraspecific antibody construct called MX851. MX851 was analyzed for binding to CD3, CD28, and BCMA by biolayer interferometry (BLI) (Figure 45B), and for binding to CD20 by flow cytometry (Figure 45C). [Figure 46A] Figure 46A shows a further non-limiting example of a tetraspecific antibody construct called MX853. MX853 was analyzed for binding to CD3, CD28, and BCMA by biolayer interferometry (BLI) (Figure 46B), and CD20 by flow cytometry (Figure 46C). [Figure 46B]Figure 46A shows a further non-limiting example of a tetraspecific antibody construct called MX853. MX853 was analyzed for binding to CD3, CD28, and BCMA by biolayer interferometry (BLI) (Figure 46B), and CD20 by flow cytometry (Figure 46C). [Figure 46C] Figure 46A shows a further non-limiting example of a tetraspecific antibody construct called MX853. MX853 was analyzed for binding to CD3, CD28, and BCMA by biolayer interferometry (BLI) (Figure 46B), and CD20 by flow cytometry (Figure 46C). [Figure 47] Figure 1 shows T cell killing of mantle cell lymphoma cell line Z-138 mediated by tetravalent tetraspecific MX851 (A) and tetravalent trispecific MX855 (B). [Figure 48A] Figure 48A shows a further non-limiting example of a trispecific antibody construct called MX894 (VRC01scFv / PGT121x10e8v4L1IgG1LS). MX894 was analyzed by biolayer interferometry (BLI) for binding to the 10e8 fusion peptide (Figure 48B), and to CD4 site-dependent (Figure 48C) and CD4 site-independent (Figure 48D) HIV spike protein. [Figure 48B] Figure 48A shows a further non-limiting example of a trispecific antibody construct called MX894 (VRC01scFv / PGT121x10e8v4L1IgG1LS). MX894 was analyzed by biolayer interferometry (BLI) for binding to the 10e8 fusion peptide (Figure 48B), and to CD4 site-dependent (Figure 48C) and CD4 site-independent (Figure 48D) HIV spike protein. [Figure 48C] Figure 48A shows a further non-limiting example of a trispecific antibody construct called MX894 (VRC01scFv / PGT121x10e8v4L1IgG1LS). MX894 was analyzed by biolayer interferometry (BLI) for binding to the 10e8 fusion peptide (Figure 48B), and to CD4 site-dependent (Figure 48C) and CD4 site-independent (Figure 48D) HIV spike protein. [Figure 48D] Figure 48A shows a further non-limiting example of a trispecific antibody construct called MX894 (VRC01scFv / PGT121x10e8v4L1IgG1LS). MX894 was analyzed by biolayer interferometry (BLI) for binding to the 10e8 fusion peptide (Figure 48B), and to CD4 site-dependent (Figure 48C) and CD4 site-independent (Figure 48D) HIV spike protein. [Figure 49A] Figure 49A shows a further non-limiting example of a tetraspecific antibody construct designated MX873 (VRC26.25x10-1074L9 / VRC01xPGT121L1 IgG1LS). MX873 was analyzed for CD4 site-dependent (Figure 49B) and CD4 site-independent (Figure 49C) binding to the HIV spike protein by biolayer interferometry (BLI). [Figure 49B] Figure 49A shows a further non-limiting example of a tetraspecific antibody construct designated MX873 (VRC26.25x10-1074L9 / VRC01xPGT121L1 IgG1LS). MX873 was analyzed for CD4 site-dependent (Figure 49B) and CD4 site-independent (Figure 49C) binding to the HIV spike protein by biolayer interferometry (BLI). [Figure 49C] Figure 49A shows a further non-limiting example of a tetraspecific antibody construct designated MX873 (VRC26.25x10-1074L9 / VRC01xPGT121L1 IgG1LS). MX873 was analyzed for CD4 site-dependent (Figure 49B) and CD4 site-independent (Figure 49C) binding to the HIV spike protein by biolayer interferometry (BLI). [Figure 50A] Figure 50A shows a further non-limiting example of a tetraspecific antibody construct designated MX875 (10-1074xVRC26.25L9 / VRC01xPGT121L1 IgG1LS). MX875 was analyzed for CD4 site-dependent (Figure 50B) and CD4 site-independent (Figure 50C) binding to the HIV spike protein by biolayer interferometry (BLI). [Figure 50B]Figure 50A shows a further non-limiting example of a tetraspecific antibody construct designated MX875 (10-1074xVRC26.25L9 / VRC01xPGT121L1 IgG1LS). MX875 was analyzed for CD4 site-dependent (Figure 50B) and CD4 site-independent (Figure 50C) binding to the HIV spike protein by biolayer interferometry (BLI). [Figure 50C] Figure 50A shows a further non-limiting example of a tetraspecific antibody construct designated MX875 (10-1074xVRC26.25L9 / VRC01xPGT121L1 IgG1LS). MX875 was analyzed for CD4 site-dependent (Figure 50B) and CD4 site-independent (Figure 50C) binding to the HIV spike protein by biolayer interferometry (BLI). [Figure 51A] Figure 51A shows a further non-limiting example of a tetraspecific antibody construct called MX877 (STAR_VRC26.25xPGT128L9 / STAR_VRC01xPGT121L1 IgG1LS). MX877 was analyzed for CD4 site-dependent (Figure 51B) and CD4 site-independent (Figure 51C) binding to the HIV spike protein by biolayer interferometry (BLI). [Figure 51B] Figure 51A shows a further non-limiting example of a tetraspecific antibody construct called MX877 (STAR_VRC26.25xPGT128L9 / STAR_VRC01xPGT121L1 IgG1LS). MX877 was analyzed for CD4 site-dependent (Figure 51B) and CD4 site-independent (Figure 51C) binding to the HIV spike protein by biolayer interferometry (BLI). [Figure 51C] Figure 51A shows a further non-limiting example of a tetraspecific antibody construct called MX877 (STAR_VRC26.25xPGT128L9 / STAR_VRC01xPGT121L1 IgG1LS). MX877 was analyzed for CD4 site-dependent (Figure 51B) and CD4 site-independent (Figure 51C) binding to the HIV spike protein by biolayer interferometry (BLI). DETAILED DESCRIPTION OF THE INVENTION

[0042] Detailed Description of the Invention The present invention is directed to antigen-binding polypeptides and antigen-binding polypeptide complexes (e.g., antibodies or antigen-binding fragments thereof) with improved characteristics. In some aspects, the present invention allows for the generation of multispecific and multifunctional antigen-binding polypeptides and antigen-binding polypeptide complexes through the expression of complementary self-assembling heavy and light chains expressed with a single polypeptide per arm, and, optionally, the addition of specific amino acid linkers. Because of this multifunctionality, the antigen-binding polypeptides and antigen-binding polypeptide complexes of the present invention can bind to specific combinations of target molecules for selectivity or amplification / neutralization, bring together two or more cell types, bring together targets to deliver activation signals, modify the disease microenvironment, and improve binding affinity for improved efficacy.

[0043] Throughout the specification and claims, various terms relating to aspects of the present disclosure are used. Unless otherwise indicated, such terms shall be given their ordinary meaning in the art. Other terms that are specifically defined shall be construed in a manner consistent with the definition set forth herein.

[0044] A.Definition As used herein, the term "antigen-binding polypeptide" refers to a polypeptide that has the ability to specifically bind to one or more substances (i.e., one or more antigens or epitopes) that induce an immune response.

[0045] As used herein, the term "antigen-binding polypeptide complex" refers to a group of two, three, four, or more associated polypeptides, where at least one polypeptide has the ability to specifically bind to one or more antigens. Antigen-binding polypeptide complexes include, but are not limited to, antibodies or antigen-binding fragments thereof.

[0046] The term "antibody" includes, but is not limited to, a glycoprotein immunoglobulin that specifically binds an antigen and comprises at least two heavy (H) chains and two light (L) chains interconnected by disulfide bonds. Each H chain comprises a heavy chain variable region (abbreviated herein as VH) and a heavy chain constant region. The heavy chain constant region comprises three constant domains, CH1, CH2, and CH3. Each light chain comprises a light chain variable region (abbreviated herein as VL) and a light chain constant region. The light chain constant region comprises one constant domain, CL. The VH and VL regions can be further subdivided into regions of hypervariability, termed complementarity-determining regions (CDRs), interspersed with more conserved regions, termed framework regions (FRs). Each VH and VL comprises three CDRs and four FRs, arranged from amino terminus to carboxy terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The variable regions of the heavy and light chains contain binding domains that interact with antigens. The constant regions of the antibody can mediate the binding of the immunoglobulin to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (C1q) of the classical complement system. The heavy chain may or may not have a C-terminal lysine. Unless otherwise specified herein, amino acids in the variable regions are numbered using the Kabat numbering system, and amino acids in the constant regions are numbered using the EU system.

[0047] The term "monoclonal antibody," as used herein, refers to an antibody produced by a single clone of B cells and that binds to the same epitope. In contrast, the term "polyclonal antibody" refers to a population of antibodies produced by different B cells and that bind to different epitopes of the same antigen. The term "antibody" includes, by way of example, monoclonal and polyclonal antibodies, chimeric and humanized antibodies, human or non-human antibodies, fully synthetic antibodies, and single-chain antibodies. Non-human antibodies can be humanized by recombinant methods to reduce their immunogenicity in humans.

[0048] The antibody may be an altered antibody (e.g., by mutation, deletion, substitution, conjugation to a non-antibody moiety). For example, the antibody may contain one or more variant amino acids that alter the properties (e.g., functional properties) of the antibody (compared to a naturally occurring antibody). For example, several such alterations are known in the art, affecting, for example, half-life, effector functions, and / or the immune response to the antibody in a patient. The term antibody also includes artificial polypeptide constructs that contain an antigen-binding site derived from at least one antibody.

[0049] An "antigen-binding fragment" of an antibody refers to one or more fragments or portions of an antibody that retain the ability to specifically bind to the antigen bound by the whole antibody. It has been shown that the antigen-binding function of an antibody can be performed by fragments or portions of a full-length antibody. An antigen-binding fragment may contain the antigen-determining region (e.g., complementarity-determining region (CDR)) of the intact antibody. Examples of antigen-binding fragments of antibodies include, but are not limited to, Fab, Fab', F(ab')2, and Fv fragments, linear antibodies, and single-chain antibodies. Antigen-binding fragments of antibodies can be derived from any animal species, such as rodents (e.g., mice, rats, or hamsters) and humans, or can be artificially produced.

[0050] Furthermore, although the two domains of the Fv fragment, VL and VH, are encoded by separate genes, they can be linked by a synthetic linker that allows them to be produced using recombinant methods as a single protein chain (known as a single-chain Fv (scFv), see, e.g., Bird et al. (1988) Science 242:423-426, and Huston et al. (1988) Proc. Natl. Acad. Sci. USA 85:5879-5883), allowing the VL and VH regions to pair to form a monovalent molecule. Such single-chain antibodies are also intended to be encompassed within the term "antigen-binding fragment" of an antibody.

[0051] Antigen-binding fragments are obtained using conventional techniques known to those of skill in the art, and the fragments are screened for utility in the same manner as are intact antibodies. Antigen-binding fragments can be produced by recombinant DNA techniques or by enzymatic or chemical cleavage of intact immunoglobulins.

[0052] As used herein, the term "variable region" typically refers to a portion of an antibody, generally a portion of either the light or heavy chain, typically the amino-terminal approximately 110-120 amino acids, or 110-125 amino acids in mature heavy chains and approximately 90-115 amino acids in mature light chains, which vary significantly in sequence among antibodies and are responsible for the binding and specificity of a particular antibody to its particular antigen. Sequence variability is concentrated in these regions, called complementarity-determining regions (CDRs), while more highly conserved regions within the variable domain are called framework regions (FRs). While not wishing to be bound by any particular mechanism or theory, it is believed that the CDRs of the light and heavy chains are primarily responsible for the interaction and specificity of the antibody with the antigen. In some embodiments, the variable region is a mammalian variable region, e.g., a human, mouse, or rabbit variable region. In some embodiments, the variable region comprises rodent or mouse CDRs and human framework regions (FRs). In some embodiments, the variable region is a primate (e.g., non-human primate) variable region. In some embodiments, the variable region comprises rodent or murine CDRs and primate (e.g., non-human primate) framework regions (FRs).

[0053] As used herein, the term "complementarity determining region" or "CDR" refers to each of the regions of an antibody variable domain that are hypervariable in sequence and / or form structurally defined loops (hypervariable loops) and / or contain antigen-contacting residues. An antibody may contain six CDRs, e.g., three in the VH and three in the VL.

[0054] The terms "VL," "VL region," and "VL domain" are used interchangeably herein to refer to a light chain variable region of an antigen-binding polypeptide, antigen-binding polypeptide complex, antibody, or antigen-binding fragment thereof. In some aspects, a VL region is referred to herein as VL1, which denotes a first light chain variable region, VL2, which denotes a second light chain variable region, VL3, which denotes a third light chain variable region, etc. A listed VL region (e.g., VL1) may have the same or different antigen-binding characteristics, and / or the same or different sequence, as another listed VL region (e.g., VL2).

[0055] The terms "VH," "VH region," and "VH domain" are used interchangeably herein to refer to the heavy chain variable region of an antigen-binding polypeptide, antigen-binding polypeptide complex, antibody, or antigen-binding fragment thereof. In some aspects, a VH region is referred to herein as VH1, which denotes a first heavy chain variable region, VH2, which denotes a second heavy chain variable region, VH3, which denotes a third heavy chain variable region, etc. A listed VH region (e.g., VH1) may have the same or different antigen-binding characteristics, and / or the same or different sequence, as another listed VH region (e.g., VH2).

[0056] As used herein, "Kabat numbering" and similar terms are art-recognized and refer to a numbering system for amino acid residues in the heavy and light chain variable regions of an antibody or antigen-binding fragment thereof. In some embodiments, CDRs can be determined according to the Kabat numbering system (see, e.g., Kabat EA & Wu TT (1971) Ann. NY Acad. Sci. 190:382-391 and Kabat EA et al., (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, USDapartment of Health and Human Services, NIH Publication No. 91-3242). Using the Kabat numbering system, the CDRs in an antibody heavy chain molecule are typically located at amino acid positions 31-35, followed by 35 (designated 35A and 35B in the Kabat numbering scheme) (CDR1), which may optionally contain one or two additional amino acids, at amino acid positions 50-65 (CDR2), and at amino acid positions 95-102 (CDR3). Using the Kabat numbering system, the CDRs in an antibody light chain molecule are typically located at amino acid positions 24-34 (CDR1), at amino acid positions 50-56 (CDR2), and at amino acid positions 89-97 (CDR3).

[0057] As used herein, the terms "constant region" or "constant domain" are used interchangeably to refer to a portion of an antigen-binding polypeptide, antigen-binding polypeptide complex, antibody, or antigen-binding fragment thereof, e.g., the carboxyl-terminal portion of the light chain and / or heavy chain, which is not directly involved in binding the antibody to an antigen but can exhibit various effector functions, such as interacting with the Fc region. Constant regions generally have a more conserved amino acid sequence compared to the variable region. In some embodiments, an antigen-binding polypeptide, antigen-binding polypeptide complex, antibody, or antigen-binding fragment thereof comprises a constant region, or portion thereof, sufficient for antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC).

[0058] As used herein, the terms "fragment crystallizable region," "Fc region," or "Fc domain" are used interchangeably herein to refer to the tail region of an antibody that interacts with cell surface receptors called Fc receptors and several proteins of the complement system. The Fc region typically includes CH2 and CH3 regions and, optionally, an immunoglobulin hinge. Examples of Fc regions include, but are not limited to, the amino acid sequence of any one of SEQ ID NOs: 389-402, or an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to any one of SEQ ID NOs: 389-402. Examples of CH2 regions include, but are not limited to, the amino acid sequence of any one of SEQ ID NOs: 408-413, or an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to any one of SEQ ID NOs: 408-413. Examples of CH3 regions include, but are not limited to, the amino acid sequence of any one of SEQ ID NOs: 414-417, or an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to any one of SEQ ID NOs: 414-417.

[0059] As used herein, the terms "immunoglobulin hinge," "hinge," "hinge domain," or "hinge region" are used interchangeably to refer to the region of an antigen-binding polypeptide, antigen-binding polypeptide complex, or heavy chain between the Fab and Fc portions of an antibody or antigen-binding fragment thereof. The hinge provides structure, positioning, and flexibility, aiding in the normal function of the antibody (e.g., for cross-linking two antigens or binding two antigenic determinants on the same antigen molecule). Immunoglobulin hinges are divided into upper, middle, and lower hinge regions, which can be separated based on structural and / or genetic components. Immunoglobulin hinges of the present invention may contain one, two, or all three of these regions. Structurally, the upper hinge region extends from the C-terminal end of CH1 to the first hinge disulfide bond. The middle hinge region extends from the first cysteine ​​to the last cysteine ​​in the hinge. The lower hinge region extends from the last cysteine ​​to the glycine of CH2. The cysteines present in the hinge form the interchain disulfide bonds that link the immunoglobulin monomers.

[0060] As used herein, the term "Fab" refers to the region of an antibody that binds to an antigen, typically consisting of one constant domain and one variable domain from each of the heavy and light chains.

[0061] As used herein, the term "heavy chain" refers to an antigen-binding polypeptide, antigen-binding polypeptide complex, antibody, or antigen-binding fragment thereof, typically composed of a heavy chain variable region (VH), heavy chain constant region 1 (CH1), heavy chain constant region 2 (CH2), and heavy chain constant region 3 (CH3). A typical antibody is composed of two heavy chains and two light chains. When used in reference to an antibody, heavy chain can refer to any distinct type, e.g., alpha (α), delta (δ), epsilon (ε), gamma (γ), and mu (μ), based on the amino acid sequence of the constant region, which gives rise to antibodies of the IgA, IgD, IgE, IgG, and IgM classes, respectively, including subclasses of IgG, e.g., IgG1, IgG2, IgG3, and IgG4. Heavy chain amino acid sequences are known in the art. In some embodiments, the heavy chain is a human heavy chain.

[0062] As used herein, the term "light chain" refers to a portion of an antigen-binding polypeptide, antigen-binding polypeptide complex, antibody, or antigen-binding fragment thereof, typically composed of a light chain variable region (VL) and a light chain constant region (CL). A typical antibody is composed of two light chains and two heavy chains. When used in reference to an antibody, light chain may refer to any distinct type, e.g., kappa (κ) or lambda (λ), based on the amino acid sequence of the constant region. Light chain amino acid sequences are known in the art. In some embodiments, the light chain is a human light chain.

[0063] The term "chimeric" antibody or antigen-binding fragment thereof refers to an antibody or antigen-binding fragment thereof whose amino acid sequences are derived from two or more species. Typically, the variable regions of both the light and heavy chains correspond to the variable regions of an antibody or antigen-binding fragment thereof from one species of mammal (e.g., mouse, rat, rabbit, etc.) having the desired specificity, affinity, and capacity, while the constant regions are homologous to the sequences of an antibody or antigen-binding fragment thereof from another species (usually human) to avoid eliciting an immune response in that species.

[0064] The term "humanized" antibody or antigen-binding fragment thereof refers to a form of a non-human (e.g., murine) antibody or specific immunoglobulin chain antigen-binding fragment, chimeric immunoglobulin, or fragment thereof that contains minimal non-human (e.g., murine) sequence. Typically, humanized antibodies or antigen-binding fragments thereof are human immunoglobulins in which residues from the complementarity-determining regions (CDRs) are replaced by residues from the CDRs of a non-human species (e.g., mouse, rat, rabbit, hamster) having the desired specificity, affinity, and capacity (Jones et al., Nature 321:522-525 (1986); Riechmann et al., Nature 332:323-327 (1988); Verhoeyen et al., Science 239:1534-1536 (1988)). In some embodiments, Fv framework region (FR) residues of a human immunoglobulin are replaced with corresponding residues in an antibody or fragment from a non-human species having the desired specificity, affinity, and capacity. To improve and optimize the specificity, affinity, and / or capacity of the antibody or antigen-binding fragment, the humanized antibody or antigen-binding fragment can be further modified by substitution of additional residues within the Fv framework regions and / or the replaced non-human residues. Generally, a humanized antibody or antigen-binding fragment will comprise substantially all of at least one, typically two or three, variable domains containing all or substantially all of the CDR regions corresponding to the non-human immunoglobulin, while all or substantially all of the FR regions are of human immunoglobulin consensus sequences. The humanized antibody or antigen-binding fragment may also comprise at least a portion of a constant region, typically that of a human immunoglobulin. Examples of methods used to generate humanized antibodies are known and are described, for example, in U.S. Pat. No. 5,225,539, Roguska et al., Proc. Natl. Acad. Sci., USA, 91(3):969-973 (1994), and Roguska et al., Protein Eng. 9(10):895-904 (1996).

[0065] As used herein, the term "human" antibody or antigen-binding fragment thereof means an antibody or antigen-binding fragment thereof having an amino acid sequence derived from the human immunoglobulin locus, and such an antibody or antigen-binding fragment is produced using recombinant techniques known in the art. This definition of a human antibody or antigen-binding fragment thereof includes intact or full-length antibodies and fragments thereof.

[0066] An "isolated" polypeptide, polypeptide complex, antibody, antigen-binding fragment thereof, polynucleotide, vector, or host cell is a polypeptide, polypeptide complex, antibody, antigen-binding fragment thereof, polynucleotide, vector, or host cell that is in a form not found in nature. Isolated polypeptides, polypeptide complexes, antibodies, antigen-binding fragments thereof, polynucleotides, vectors, or host cells include those that have been purified to the extent that they are no longer in the form in which they are found in nature. In some embodiments, an isolated polypeptide, polypeptide complex, antibody, antigen-binding fragment thereof, polynucleotide, vector, or host cell is substantially pure. As used herein, "substantially pure" refers to material that is at least 50% pure (i.e., free from contaminants), at least 90% pure, at least 95% pure, at least 98% pure, or at least 98% pure.

[0067] The terms "polypeptide," "peptide," and "protein" are used interchangeably herein to refer to polymers of amino acids of any length. Polymers can be linear or branched, can comprise modified amino acids, and can be interrupted by non-amino acids. These terms also encompass amino acid polymers, whether naturally occurring or modified by intervention, e.g., disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification, such as conjugation with a labeling component. Also included within the definition are polypeptides containing, for example, one or more analogs of an amino acid (including, e.g., unnatural amino acids), as well as other modifications known in the art. Because the polypeptides of the present invention are based on antibodies, it is understood that in some aspects the polypeptides can occur as single chains or associated chains.

[0068] The use of the alternative (e.g., "or") should be understood to mean either one, both, or any combination thereof of the alternatives. As used herein, the indefinite article "a" or "an" should be understood to refer to "one or more" of any shown or listed components.

[0069] As used herein, the term "and / or" is to be construed as a specific disclosure of each of the two specified features or components, with or without the other features or components. Thus, as used herein, the term "and / or" when used in phrases such as "A and / or B" is intended to include "A and B," "A or B," "A" (alone), and "B" (alone). Similarly, the term "and / or" when used in phrases such as "A, B, and / or C" is intended to encompass each of the following aspects: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone).

[0070] In all cases, embodiments are described herein using language such as "comprising," "having," and the like, but analogous embodiments described with the terms "consisting of" and / or "consisting essentially of" are also provided.

[0071] As used herein, the term "about" refers to a value or composition that is within an acceptable error range for a particular value or composition, as determined by one of ordinary skill in the art, and will depend in part on how the value or composition is measured or determined, i.e., the limitations of the measurement system. For example, "about" can mean within 1 or more standard deviations, as is customary in the art. Alternatively, "about" can mean a range of up to 10% or 20% (i.e., ±10% or ±20%). For example, approximately 3 mg can refer to any number between 2.7 mg and 3.3 mg (10%), or between 2.4 mg and 3.6 mg (20%). Furthermore, specifically with respect to biological systems or processes, the term can mean up to an order of magnitude, or up to five times the value. When a particular value or composition is provided in this application and claims, unless otherwise specified, the meaning of "about" should be assumed to be within an acceptable error range for that particular value or composition.

[0072] As described herein, any numerical range, concentration range, percentage range, ratio range, or integer range, unless otherwise indicated, is understood to include any integer value within the stated range, and, where appropriate, fractions thereof (such as integer tenths and hundredths).

[0073] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. For example, the Concise Dictionary of Biomedicine and Molecular Biology, Juo, Pei-Show, 2nd ed., 2002, CRC Press, The Dictionary of Cell and Molecular Biology, 5th ed., 2013, Academic Press, and the Oxford Dictionary of Biochemistry and Molecular Biology, 2006, Oxford University Press provide those skilled in the art with a general dictionary of many of the terms used in this disclosure.

[0074] Units, prefixes, and symbols are denoted in the format accepted by the Systeme International de Unites (SI). Numerical ranges are intended to be inclusive of the numbers defining the range. The headings provided herein are not limitations of the various aspects of the disclosure, which may be had by reference to the specification as a whole. Accordingly, terms defined herein are more fully defined by reference to the specification as a whole.

[0075] Various aspects are described in further detail in the following paragraphs.

[0076] Antigen-binding polypeptides and antigen-binding polypeptide complexes In some aspects, the present invention is directed to antigen-binding polypeptides and antigen-binding polypeptide complexes that have certain structural characteristics.

[0077] In some aspects, the invention is directed to an antigen-binding polypeptide or antigen-binding polypeptide complex comprising a polypeptide having a structure represented by VL1-VL2-VL3-VH3-VH2-VH1, VH1-VH2-VH3-VL3-VL2-VL1, VL1-VH2-VL3-VH3-VL2-VH1, VH1-VL2-VH3-VL3-VH2-VL1, VL1-VL2-VH3-VL3-VH2-VH1, VL1-VL2-VH3-VL3-VH2-VH1, VH1-VH2-VL3-VH3-VL2-VL1, VL1-VH2-VH3-VL3-VL2-VH1, or VH1-VL2-VL3-VH3-VH2-VL1. In some embodiments, the antigen-binding polypeptide or antigen-binding polypeptide complex contains an amino acid linker between any two regions shown in the structures described herein. In some embodiments, the antigen-binding polypeptide or antigen-binding polypeptide complex may contain an Fc region, a CH1 region, a CL region, a CH3 region, or any combination thereof. In some embodiments, the Fc region, the CH1 region, the CL region, and / or the CH3 region are located at the carboxy terminus of the antigen-binding polypeptide and are optionally linked to the polypeptide by at least one amino acid linker. In some embodiments, the Fc region comprises the amino acid sequence of any one of SEQ ID NOs: 389-402, or an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to any one of SEQ ID NOs: 389-402. In some embodiments, the CH1 region comprises the amino acid sequence of any one of SEQ ID NOs: 403-407, or an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to any one of SEQ ID NOs: 403-407.In some embodiments, the CL region comprises the amino acid sequence of SEQ ID NO: 418 or 419, or an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO: 418 or 419. In some embodiments, the antigen-binding polypeptide complex is an antibody or antigen-binding fragment thereof.

[0078] In some embodiments, an antigen-binding polypeptide or antigen-binding polypeptide complex of the invention comprises VL1-VL2-VL3-VH3-VH2-VH1, VH1-VH2-VH3-VL3-VL2-VL1, VL1-VH2-VL3-VH3-VL2-VH1, VH1-VL2-VH3-VL3-VH2-VL1, VL1-VL2-VH3-VL3-VH2-VL1, VL1-VL2-VH3-VL3-VH2-VH1, VH1-VH2-VL3-VH3-VL2-VL1, VL1 -VH2-VH3-VL3-VL2-VH1, VH1-VL2-VL3-VH3-VH2-VL1, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1, VH1-L1-VH2 -L2-VH3-L3-VL3-L4-VL2-L5-VL1, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1, VH1-L1-VL2-L2-VH3-L3-VL3-L4 -VH2-L5-VL1, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1, or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1. wherein VL1 is a first immunoglobulin light chain variable region, VL2 is a second immunoglobulin light chain variable region, VL3 is a third immunoglobulin light chain variable region, VH1 is a first immunoglobulin heavy chain variable region, VH2 is a second immunoglobulin heavy chain variable region, VH3 is a third immunoglobulin heavy chain variable region, and L1, L2, L3, L4, and L5 are amino acid linkers.

[0079] In some aspects, the antigen-binding polypeptide complex comprises a first polypeptide and a second polypeptide, wherein the first polypeptide is selected from the group consisting of: VL1-VL2-VL3-VH3-VH2-VH1, VH1-VH2-VH3-VL3-VL2-VL1, VL1-VH2-VL3-VH3-VL2-VH1, VH1-VL2-VH3-VL3-VH2-VL1, VL1-VL2-VH3-VL3-VH2-VH1, VL1-VL2-VH3-VL3-VH2-VH1, VH1-VH2-VL3-VH3-VL2-VL1, VL1-VH2-VH3-VL3-VL2-VH1, VL1-VH2-VL3-VH ...3-VL2-VH1, VH1-VL2-VL3-VH 3-VH2-VL1, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1, VH1-L1-VH2- L2-VH3-L3-VL3-L4-VL2-L5-VL1, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L 5-VH1, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1, VL1-L1-VL2-L2-VH 3-L3-VL3-L4-VH2-L5-VH1, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1 , VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1, or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-L6-VH4, VH4-L6-VL4, VL4-L6-VH4-L7, VH4-L6-VL4-L7, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-L6-VL5-L7-VH5-L8-VH4, VH4-L6-VH5-L7- VL5-L8-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, V L4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL 6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, VH4 -VL5-VL6-VH6-VH5-VL4, VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4,VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4, VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4, VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4, V H4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4, or VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4, wherein VL1 is a first immunoglobulin light chain variable region. VL2 is a second immunoglobulin light chain variable region, VL3 is a third immunoglobulin light chain variable region, VL4 is a fourth immunoglobulin light chain variable region, VL5 is a fifth immunoglobulin light chain variable region, VL6 is a sixth immunoglobulin light chain variable region, VH1 is a first immunoglobulin heavy chain variable region, VH2 is a second immunoglobulin heavy chain variable region, VH3 is a third immunoglobulin heavy chain variable region, VH4 is a fourth immunoglobulin heavy chain variable region, VH5 is a fifth immunoglobulin heavy chain variable region, VH6 is a sixth immunoglobulin heavy chain variable region, and L1, L2, L3, L4, L5, L6, L7, L8, L9, and L10 are amino acid linkers. In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VL3-VH3-VH2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-L6-VH4, VH4-L6-VL4, VL4-L6-VH4-L7, VH4-L6-VL4-L7, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, V L4-L6-VL5-L7-VH5-L8-VH4, VH4-L6-VH5-L7-VL5-L8-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6 -VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4,VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, VH4-VL5-VL6-VH6-VH5-VL4, VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH 5-L10-VH4, VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4, VH4-L6-VL5-L 7-VH6-L8-VL6-L9-VH5-L10-VL4, VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4, VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4, or VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4. In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VH3-VL3-VL2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-L6-VH4, VH4-L6-VL4, VL4-L6-VH4-L7, VH4-L6-VL4-L7, VL4-VL5 -VH5-VH4, VH4-VH5-VL5-VL4, VL4-L6-VL5-L7-VH5-L8-VH4, VH4-L6-VH5-L7-VL5-L8- VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5 -VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL 5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, VH4-VL5-VL6-VH6-VH5-VL4, VL4-L6-VL5-L7-VL6 -L8-VH6-L9-VH5-L10-VH4, VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4, VL4-L6-V H5-L7-VL6-L8-VH6-L9-VL5-L10-VH4, VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4,VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4, VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4, or VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4. In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VL3-VH3-VL2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-L6-VH4, VH4-L6-VL4, VL4-L6-VH4-L7, VH4-L6-VL4-L7, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-L6-VL5-L7-VH5-L 8-VH4, VH4-L6-VH5-L7-VL5-L8-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH 6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6- VL6-VL5-VH4, VH4-VL5-VL6-VH6-VH5-VL4, VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4, VH4-L6-VH5-L7-VH6 -L8-VL6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4, VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VH3-VL3-VH2-VL1 and the second polypeptide has a structure represented by VL4-VH4, VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4, VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4, or VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4.VH4-VL4, VL4-L6-VH4, VH4-L6-VL4, VL4-L6-VH4-L7, VH4-L6-VL4-L7, VL4-VL5-VH5-VH4, VH4-VH5-V L5-VL4, VL4-L6-VL5-L7-VH5-L8-VH4, VH4-L6-VH5-L7-VL5-L8-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4 -VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL 6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, VH4-VL5-VL6-VH6-VH5-VL4, VL 4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4, VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4, VL4-L 6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4, VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4, VL4-L6-VL VH4-L6-VH5-L7-VL6-L8-VH6-L9-VH5-L10-VH4, VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4, or VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4. In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VH3-VL3-VH2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-L6-VH4, VH4-L6-VL4, VL4-L6-VH4-L7, VH4-L6-VL4-L7, VL4-VL5-VH5-VH4, VH4-VH1 H5-VL5-VL4, VL4-L6-VL5-L7-VH5-L8-VH4, VH4-L6-VH5-L7-VL5-L8-VL4, VL4-VL5-VL6-VH6-V H5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4,VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, VH4-VL5-VL6-VH6-VH5-VL4, VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4, VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4, VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4, VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4, VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4, or VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4. In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VL3-VH3-VL2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-L6-VH4, VH4-L6-VL4, VL4-L6-VH4-L7, VH4-L6-VL4-L7, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-L6-VL5-L7-VH5-L 8-VH4, VH4-L6-VH5-L7-VL5-L8-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH 6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6- VL6-VL5-VH4, VH4-VL5-VL6-VH6-VH5-VL4, VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4, VH4-L6-VH5-L7-VH6 -L8-VL6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4, VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH VH4-L6-VH5-L7-VL6-L8-VH6-L9-VH5-L10-VH4, VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4, or VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4.In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VH3-VL3-VL2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-L6-VH4, VH4-L6-VL4, VL4-L6-VH4-L7, VH4-L6-VL4-L7, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-L6-VL5-L7-VH5-L 8-VH4, VH4-L6-VH5-L7-VL5-L8-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH 6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6- VL6-VL5-VH4, VH4-VL5-VL6-VH6-VH5-VL4, VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4, VH4-L6-VH5-L7-VH6 -L8-VL6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4, VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH VH4-L6-VH5-L7-VL6-L8-VH6-L9-VH5-L10-VH4, VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4, or VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4.In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VL3-VH3-VH2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-L6-VH4, VH4-L6-VL4, VL4-L6-VH4-L7, VH4-L6-VL4-L7, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-L6-VL5-L7-VH5-L 8-VH4, VH4-L6-VH5-L7-VL5-L8-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH 6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6- VL6-VL5-VH4, VH4-VL5-VL6-VH6-VH5-VL4, VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4, VH4-L6-VH5-L7-VH6 -L8-VL6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4, VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH VH4-L6-VH5-L7-VL6-L8-VH6-L9-VH5-L10-VH4, VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4, or VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4.In some embodiments, the first polypeptide has a structure represented by VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-L6-VH4, VH4-L6-VL4, VL4-L6-VH4-L7, VH4-L6-VL4-L7, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-L6-VH4 L5-L7-VH5-L8-VH4, VH4-L6-VH5-L7-VL5-L8-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-V H5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4- VH5-VH6-VL6-VL5-VH4, VH4-VL5-VL6-VH6-VH5-VL4, VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4, VH4-L6-VH5- L7-VH6-L8-VL6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4, VH4-L6-VL5-L7-VH6-L8-VL6-L VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4, VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4, or VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4.In some embodiments, the first polypeptide has a structure represented by VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-L6-VH4, VH4-L6-VL4, VL4-L6-VH4-L7, VH4-L6-VL4-L7, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-L6-VH4-L7, L5-L7-VH5-L8-VH4, VH4-L6-VH5-L7-VL5-L8-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-V H5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4- VH5-VH6-VL6-VL5-VH4, VH4-VL5-VL6-VH6-VH5-VL4, VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4, VH4-L6-VH5- L7-VH6-L8-VL6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4, VH4-L6-VL5-L7-VH6-L8-VL6-L VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4, VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4, or VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4.In some embodiments, the first polypeptide has a structure represented by VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-L6-VH4, VH4-L6-VL4, VL4-L6-VH4-L7, VH4-L6-VL4-L7, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-L6-VH4 L5-L7-VH5-L8-VH4, VH4-L6-VH5-L7-VL5-L8-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-V H5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4- VH5-VH6-VL6-VL5-VH4, VH4-VL5-VL6-VH6-VH5-VL4, VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4, VH4-L6-VH5- L7-VH6-L8-VL6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4, VH4-L6-VL5-L7-VH6-L8-VL6-L VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4, VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4, or VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4.In some embodiments, the first polypeptide has a structure represented by VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-L6-VH4, VH4-L6-VL4, VL4-L6-VH4-L7, VH4-L6-VL4-L7, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-L 6-VL5-L7-VH5-L8-VH4, VH4-L6-VH5-L7-VL5-L8-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-V. L4, VL4-VH5-VH6-VL6-VL5-VH4, VH4-VL5-VL6-VH6-VH5-VL4, VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4, VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4, VH4-L6-VL5-L7-VH6-L8-VL 6-L9-VH5-L10-VL4、VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4、VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4、 VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4、またはVH4-L 6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4In some embodiments, the first polypeptide has a structure represented by VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-L6-VH4, VH4-L6-VL4, VL4-L6-VH4-L7, VH4-L6-VL4-L7, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-L6-VH4 L5-L7-VH5-L8-VH4, VH4-L6-VH5-L7-VL5-L8-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-V H5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4- VH5-VH6-VL6-VL5-VH4, VH4-VL5-VL6-VH6-VH5-VL4, VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4, VH4-L6-VH5- L7-VH6-L8-VL6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4, VH4-L6-VL5-L7-VH6-L8-VL6-L VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4, VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4, or VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4.In some embodiments, the first polypeptide has a structure represented by VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-L6-VH4, VH4-L6-VL4, VL4-L6-VH4-L7, VH4-L6-VL4-L7, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-L6-VH4-L7, L5-L7-VH5-L8-VH4, VH4-L6-VH5-L7-VL5-L8-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-V H5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4- VH5-VH6-VL6-VL5-VH4, VH4-VL5-VL6-VH6-VH5-VL4, VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4, VH4-L6-VH5- L7-VH6-L8-VL6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4, VH4-L6-VL5-L7-VH6-L8-VL6-L VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4, VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4, or VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4.In some embodiments, the first polypeptide has a structure represented by VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-L6-VH4, VH4-L6-VL4, VL4-L6-VH4-L7, VH4-L6-VL4-L7, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-L6-VH4 L5-L7-VH5-L8-VH4, VH4-L6-VH5-L7-VL5-L8-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-V H5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4- VH5-VH6-VL6-VL5-VH4, VH4-VL5-VL6-VH6-VH5-VL4, VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4, VH4-L6-VH5- L7-VH6-L8-VL6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4, VH4-L6-VL5-L7-VH6-L8-VL6-L VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4, VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4, or VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4.In some embodiments, the first polypeptide has a structure represented by VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-L6-VH4, VH4-L6-VL4, VL4-L6-VH4-L7, VH4-L6-VL4-L7, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-L6-VH4-L7, L5-L7-VH5-L8-VH4, VH4-L6-VH5-L7-VL5-L8-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-V H5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4- VH5-VH6-VL6-VL5-VH4, VH4-VL5-VL6-VH6-VH5-VL4, VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4, VH4-L6-VH5- L7-VH6-L8-VL6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4, VH4-L6-VL5-L7-VH6-L8-VL6-L VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4, VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4, or VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4.

[0080] In some embodiments, the antigen-binding polypeptide further comprises at least one Fc region, optionally located at its carboxy terminus, or the antigen-binding polypeptide complex further comprises at least one Fc region, optionally located at its carboxy terminus, which Fc region may be linked to the polypeptide via at least one amino acid linker. For example, the antigen-binding polypeptide or polypeptides comprised within the antigen-binding complex can be VL1-VL2-VL3-VH3-VH2-VH1-Fc, VH1-VH2-VH3-VL3-VL2-VL1-Fc, VL1-VH2-VL3-VH3-VL2-VH1-Fc, VH1-VL2-VH3-VL3-VH2-VL1-Fc, VL1-VL2-VH3-VL3-VH2-VL1-Fc, VL1-VL2-VH3-VL3-VH2-VH1-Fc, VL1-VL2-VH3-VL3-VH2-VH1-Fc, VH1-VH2-VL3-VH3-VL2-VL1-Fc, VL1- VH2-VH3-VL3-VL2-VH1-Fc, VH1-VL2-VL3-VH3-VH2-VL1-Fc, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-Fc, VL1-L1-VL2 -L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-Fc, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-Fc, VH1-L1-VH2-L2-VH3-L3-VL3-L 4-VL2-L5-VL1-L6-Fc, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-Fc, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6 -Fc, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-Fc, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-Fc, VL1-L1-VL2- L2-VH3-L3-VL3-L4-VH2-L5-VH1-Fc, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-Fc, VH1-L1-VH2-L2-VL3-L3-VH3-L 4-VL2-L5-VL1-Fc, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-Fc, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-Fc,and VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-Fc, VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-Fc, or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-Fc, where VL1 is a first immunoglobulin light chain variable region, VL2 is a second immunoglobulin light chain variable region, and VL3 is a second immunoglobulin light chain variable region. L3 is a third immunoglobulin light chain variable region, VH1 is a first immunoglobulin heavy chain variable region, VH2 is a second immunoglobulin heavy chain variable region, VH3 is a third immunoglobulin heavy chain variable region, Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge, and L1, L2, L3, L4, L5, and L6 are amino acid linkers.

[0081] In some embodiments, the antigen-binding polypeptide comprises at least two Fc regions at its carboxy terminus, or the antigen-binding polypeptide complex comprises a polypeptide comprising at least two Fc regions at its carboxy terminus. The at least two Fc regions may be linked to the polypeptide via at least one amino acid linker. The at least two Fc regions may be linked to each other via at least one amino acid linker. For example, the antigen-binding polypeptide or polypeptides comprised within the antigen-binding polypeptide complex can be VL1-VL2-VL3-VH3-VH2-VH1-Fc-Fc, VH1-VH2-VH3-VL3-VL2-VL1-Fc-Fc, VL1-VH2-VL3-VH3-VL2-VH1-Fc-Fc, VH1-VL2-VH3-VL3-VH2-VL1-Fc-Fc, VH1-VL2-VH3-VL3-VH2-VL1-Fc-Fc, VL1-VL2-VH3-VL3-VH2-VH1-Fc-Fc, VH1-VL2-VH3-VL3-VH2-VH1-Fc-Fc, VH1-VH2- VL3-VH3-VL2-VL1-Fc-Fc, VL1-VH2-VH3-VL3-VL2-VH1-Fc-Fc, VH1-VL2-VL3-VH3-VH2-VL1-Fc-Fc, VL1-L1-VL2-L2-VL3-L 3-VH3-L4-VH2-L5-VH1-Fc-Fc, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-Fc-Fc, VL1-L1-VL2-L2-VL3-L3-VH3-L4 -VH2-L5-VH1-L6-Fc-L7-Fc, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-Fc-Fc, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2- L5-VL1-L6-Fc-Fc, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-Fc-L7-Fc, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5 -VH1-Fc-Fc, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-Fc-Fc, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6- Fc-L7-Fc, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-Fc-Fc, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-Fc-Fc,VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-Fc-L7-Fc, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-Fc-Fc, VL1-L1-VL2-L2-VH3 -L3-VL3-L4-VH2-L5-VH1-L6-Fc-Fc, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-Fc-L7-Fc, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2 -L5-VL1-Fc-Fc, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-Fc-Fc, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-Fc-L7-Fc, L1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-Fc-Fc, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-Fc-Fc, VL1-L1-VH2-L2-VH3-L3- and VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-Fc-Fc, VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-Fc-Fc, VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-Fc-Fc, or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-Fc-L7-Fc, where VL1 is a first immunoglobulin light chain variable region and VL2 is a second immunoglobulin light chain variable region. VL2 is a second immunoglobulin light chain variable region, VH1 is a first immunoglobulin heavy chain variable region, VH2 is a second immunoglobulin heavy chain variable region, VH3 is a third immunoglobulin heavy chain variable region, Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge, and L1, L2, L3, L4, L5, L6, and L7 are amino acid linkers.

[0082] In some embodiments, the antigen-binding polypeptide complex comprises a first polypeptide and a second polypeptide, each comprising at least one Fc optionally located at the carboxy terminus. For example, the antigen-binding complex may comprise a first polypeptide and a second polypeptide, wherein the first polypeptide has the sequence VL1-VL2-VL3-VH3-VH2-VH1-Fc, VH1-VH2-VH3-VL3-VL2-VL1-Fc, VL1-VH2-VL3-VH3-VL2-VH1-Fc, VH1-VL2-VH3-VL3-VH2-VL1-Fc, VL1-VL2-VH3-VL3-VH2-VL1-Fc, VL1-VL2-VH3-VL3-VH2-VH1-Fc, VL1-VL2-VH3-VL3-VH2-VH1-Fc, VL1-VH2-VL3-VH3-VL2-VL1-Fc, VL1-VH2-VH3-VL3-VH2-VL1-Fc, VL1-VH2-VL3-VH3-VL2-VL1-Fc, VL1-VH2-VH3-VL3-VL 2-VH1-Fc, VH1-VL2-VL3-VH3-VH2-VL1-Fc, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-Fc, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-V H1-L6-Fc, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-Fc, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-Fc, VL1-L1-VH2-L2-VL3-L 3-VH3-L4-VL2-L5-VH1-Fc, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-Fc, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-Fc, VH1- L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-Fc, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-Fc, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2- L5-VH1-L6-Fc, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-Fc, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-Fc, VL1-L1-VH2-L2- VH3-L3-VL3-L4-VL2-L5-VH1-Fc, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-Fc, VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-Fc,or has a structure represented by VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-Fc, and the second polypeptide is Fc, VL4-VH4-Fc, VH4-VL4-Fc, VL4-L7-VH4-Fc, VL4-L7-VH4-L8-Fc, VH4-L7-VL4-Fc, VH4-L7-VL4-L8-Fc, VL4-VL5-VH5-VH4-Fc, VH4-VH5-VL5-VL4-Fc, VL4-L7-VL5-L8-VH5-L9-VH4-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-Fc, L7-VL5-L8-VH5-L9-VH4-L10-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-L10-Fc, VL4-VL5-VL6-VH6-VH5-VH4-Fc, VH4-VH5-VH6-VL6-VL5-VL4-Fc, VL4-VH5-VL6-VH6-VL5-VH4-Fc, VH4-VL5-VH6-VL6-VH5-VL4-Fc, VL4-VL5-VH6-VL6-VH5-VH4-Fc, VH4-VH5-VL6-VH6-VL5-VL4-Fc, VL4-VH5-VH6-VL6-VL5-VH4-Fc, VH4-VL5-VL6-VH6-VH5-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-Fc, VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VL6-LVL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-L12-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-L1 2-Fc, VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL and VL1 is a first immunoglobulin light chain variable region, VL2 is a second immunoglobulin light chain variable region, and VL3 is a third immunoglobulin light chain variable region. VH1 is a first immunoglobulin heavy chain variable region, VH2 is a second immunoglobulin heavy chain variable region, VH3 is a third immunoglobulin heavy chain variable region, and VH4 is a fourth immunoglobulin heavy chain variable region, VH5 is a fourth immunoglobulin light chain variable region, VH6 is a sixth immunoglobulin light chain variable region, VH1 is a first immunoglobulin heavy chain variable region, VH2 is a second immunoglobulin heavy chain variable region, VH3 is a third immunoglobulin heavy chain variable region, and VH4 is a fourth immunoglobulin heavy chain variable region. VH5 is a fifth immunoglobulin heavy chain variable region, VH6 is a sixth immunoglobulin heavy chain variable region, Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge, and L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, and L12 are amino acid linkers. In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VL3-VH3-VH2-VH1-Fc, and the second polypeptide has a structure represented by Fc, VL4-VH4-Fc, VH4-VL4-Fc, VL4-L7-VH4-Fc, VL4-L7-VH4-L8-Fc, VH4-L7-VL4-Fc, VH4-L7-VL4-L8-Fc, VL4-VL5-VH5-VH4-Fc, VH4-VH5-VL5-VL4-Fc, VL4-L7-VL5-L8-VH5-L9-VH4-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-Fc,L7-VL5-L8-VH5-L9-VH4-L10-Fc、VH4-L7-VH5-L8-VL5-L9-VL4-L10-Fc、 VL4-VL5-VL6-VH6-VH5-VH4-Fc、VH4-VH5-VH6-VL6-VL5-VL4-Fc、VL4-VH 5-VL6-VH6-VL5-VH4-Fc、VH4-VL5-VH6-VL6-VH5-VL4-Fc、VL4-VL5-VH6- VL6-VH5-VH4-Fc、VH4-VH5-VL6-VH6-VL5-VL4-Fc、VL4-VH5-VH6-VL6-VL5 -VH4-Fc、VH4-VL5-VL6-VH6-VH5-VL4-Fc、VL4-L7-VL5-L8-VL6-L9-VH6- L10-VH5-L11-VH4-Fc、VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4- Fc, VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VH6-L9-VL6-L10-V H5-L11-VH4-Fc、VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-Fc、VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-Fc、VH4-L7-VL5-L8-VL6- L9-VH6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-L12-Fc VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-L12-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-L12-Fc, VL4-L7-VL5-L8-VH6-L9-VL 6-L10-VH5-L11-VH4-L12-Fc、VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-L12-Fc、VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc、or has a structure represented by VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-L12-Fc. In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VH3-VL3-VL2-VL1-Fc, and the second polypeptide has a structure represented by any of Fc, VL4-VH4-Fc, VH4-VL4-Fc, VL4-L7-VH4-Fc, VL4-L7-VH4-L8-Fc, VH4-L7-VL4-Fc, VH4-L7-VL4-L8-Fc, VL4-VL5-VH5-VH4-Fc, VH4-VH5-VL5-VL4-Fc, VL4-L7-VL5-L8-VH5-L9-VH4-Fc, VH4-L7- VH5-L8-VL5-L9-VL4-Fc, L7-VL5-L8-VH5-L9-VH4-L10-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-L10-Fc, VL4-VL5-VL6-VH6-VH5-VH4-Fc, VH4-VH5- VH6-VL6-VL5-VL4-Fc, VL4-VH5-VL6-VH6-VL5-VH4-Fc, VH4-VL5-VH6-VL6-VH5-VL4-Fc, VL4-VL5-VH6-VL6-VH5-VH4-Fc, VH4-VH5-VL6-VH6- VL5-VL4-Fc, VL4-VH5-VH6-VL6-VL5-VH4-Fc, VH4-VL5-VL6-VH6-VH5-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-Fc, VH4-L7- VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-Fc, VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L1 1-VL4-Fc, VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-Fc, VH4-L 7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-Fc, VL4-L7-VH5-L8-VH6-L 9-VL6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5- L11-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-L12-Fc,VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-L12-Fc、VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-L12-Fc、VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-L12-Fc、VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-L12-Fc、VH4-L7、 -VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc, or VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-L12-Fc. In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VL3-VH3-VL2-VH1-Fc, and the second polypeptide has a structure represented by Fc, VL4-VH4-Fc, VH4-VL4-Fc, VL4-L7-VH4-Fc, VL4-L7-VH4-L8-Fc, VH4-L7-VL4-Fc, VH4-L7-VL4-L8-Fc, VL4-VL5-VH5-VH4-Fc, VH4-VH5-VL5-VL4-Fc, VL4-L7-VL5-L8-Fc, 8-VH5-L9-VH4-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-Fc, L7-VL5-L8-VH5-L9-VH4-L10-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-L10-Fc, VL4-VL5-VL6-VH6-VH5-VH4-Fc, VH4-VH5-VH6-VL6-VL5-VL4-Fc, VL4-VH5-VL6-VH6-VL5-VH4-Fc, VH4-VL5-VH6-VL6-VH5-VL4- Fc, VL4-VL5-VH6-VL6-VH5-VH4-Fc, VH4-VH5-VL6-VH6-VL5-VL4-Fc, VL4-VH5-VH6-VL6-VL5-VH4-Fc, VH4-VL5-VL6-VH6-VH5- VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-Fc, VL4-L7-VH5 -L8-VL6-L9-VH6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VH6-L9-VL6-L1 0-VH5-L11-VH4-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-Fc,VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VH6-L 9-VL6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-L12-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L 11-VL4-L12-Fc, VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc, or VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-L12-Fc. In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VH3-VL3-VH2-VL1-Fc, and the second polypeptide has a structure represented by Fc, VL4-VH4-Fc, VH4-VL4-Fc, VL4-L7-VH4-Fc, VL4-L7-VH4-L8-Fc, VH4-L7-VL4-Fc, VH4-L7-VL4-L8-Fc, VL4-VL5-VH5-VH4-Fc, VH4-VH5-VL5-VL4-Fc, VL4-L7-VL5-L8-VH5-L9-VH4-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-Fc, VH4-L7-VL ... H5-L9-VH4-L10-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-L10-Fc, VL4-VL5-VL6-VH6-V H5-VH4-Fc, VH4-VH5-VH6-VL6-VL5-VL4-Fc, VL4-VH5-VL6-VH6-VL5-VH4-Fc, VH 4-VL5-VH6-VL6-VH5-VL4-Fc, VL4-VL5-VH6-VL6-VH5-VH4-Fc, VH4-VH5-VL6-VH 6-VL5-VL4-Fc, VL4-VH5-VH6-VL6-VL5-VH4-Fc, VH4-VL5-VL6-VH6-VH5-VL4-Fc,VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-Fc, VL4-L7 -VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L 8-VH6-L9-VL6-L10-VH5-L11-VH4-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-Fc, VL4-L7-VH5-L8-VH6- L9-VL6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6 -L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VL6-L9-V H6-L10-VL5-L11-VH4-L12-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-L12-Fc, VL4-L7-VL5-L8-VH6-L9 -VL6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc, or VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-L12-Fc. In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VH3-VL3-VH2-VH1-Fc, and the second polypeptide has a structure represented by Fc, VL4-VH4-Fc, VH4-VL4-Fc, VL4-L7-VH4-Fc, VL4-L7-VH4-L8-Fc, VH4-L7-VL4-Fc, VH4-L7-VL4-L8-Fc, VL4-VL5-VH5-VH4-Fc, VH4-VH5-VL5-VL4-Fc, VL4-L7-VL5-L8-VH5-L9-VH4-Fc,VH4-L7-VH5-L8-VL5-L9-VL4-Fc, L7-VL5-L8-VH5-L9-VH4-L10-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-L10-Fc, VL4-VL5-VL6-VH6-VH5-VH4-Fc, VH4-VH5-V H6-VL6-VL5-VL4-Fc、VL4-VH5-VL6-VH6-VL5-VH4-Fc、VH4-VL5-VH6-VL6-V H5-VL4-Fc、VL4-VL5-VH6-VL6-VH5-VH4-Fc、VH4-VH5-VL6-VH6-VL5-VL4-F c、VL4-VH5-VH6-VL6-VL5-VH4-Fc、VH4-VL5-VL6-VH6-VH5-VL4-Fc、VL4-L7 -VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-Fc、VH4-L7-VH5-L8-VH6-L9-VL6 -L10-VL5-L11-VL4-Fc、VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-Fc、VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-Fc、VL4-L7-VL5-L8-VH 6-L9-VL6-L10-VH5-L11-VH4-Fc、VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L 11-VL4-Fc、VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-Fc、VH4-L7-V L5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4 -L12-Fc、VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-L12-Fc、VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-L12-Fc、VL4-L7-VL5-L8-VH6-L9 -VL6-L10-VH5-L11-VH4-L12-Fc、VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-L12-Fc、VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc、or has a structure represented by VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-L12-Fc. In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VL3-VH3-VL2-VL1-Fc, and the second polypeptide has a structure represented by any of Fc, VL4-VH4-Fc, VH4-VL4-Fc, VL4-L7-VH4-Fc, VL4-L7-VH4-L8-Fc, VH4-L7-VL4-Fc, VH4-L7-VL4-L8-Fc, VL4-VL5-VH5-VH4-Fc, VH4-VH5-VL5-VL4-Fc, VL4-L7-VL5-L8-VH5-L9-VH4-Fc, VH4-L7- VH5-L8-VL5-L9-VL4-Fc, L7-VL5-L8-VH5-L9-VH4-L10-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-L10-Fc, VL4-VL5-VL6-VH6-VH5-VH4-Fc, VH4-VH5- VH6-VL6-VL5-VL4-Fc, VL4-VH5-VL6-VH6-VL5-VH4-Fc, VH4-VL5-VH6-VL6-VH5-VL4-Fc, VL4-VL5-VH6-VL6-VH5-VH4-Fc, VH4-VH5-VL6-VH6- VL5-VL4-Fc, VL4-VH5-VH6-VL6-VL5-VH4-Fc, VH4-VL5-VL6-VH6-VH5-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-Fc, VH4-L7- VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-Fc, VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L1 1-VL4-Fc, VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-Fc, VH4-L 7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-Fc, VL4-L7-VH5-L8-VH6-L 9-VL6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5- L11-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-L12-Fc,VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-L12-Fc、VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-L12-Fc、VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-L12-Fc、VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-L12-Fc、 , VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc, or VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-L12-Fc. In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VH3-VL3-VL2-VH1-Fc, and the second polypeptide has a structure represented by Fc, VL4-VH4-Fc, VH4-VL4-Fc, VL4-L7-VH4-Fc, VL4-L7-VH4-L8-Fc, VH4-L7-VL4-Fc, VH4-L7-VL4-L8-Fc, VL4-VL5-VH5-VH4-Fc, VH4-VH5-VL5-VL4-Fc, VL4-L7-VL5-L8-Fc, 8-VH5-L9-VH4-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-Fc, L7-VL5-L8-VH5-L9-VH4-L10-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-L10-Fc, VL4-VL5-VL6-VH6-VH5-VH4-Fc, VH4-VH5-VH6-VL6-VL5-VL4-Fc, VL4-VH5-VL6-VH6-VL5-VH4-Fc, VH4-VL5-VH6-VL6-VH5-VL4- Fc, VL4-VL5-VH6-VL6-VH5-VH4-Fc, VH4-VH5-VL6-VH6-VL5-VL4-Fc, VL4-VH5-VH6-VL6-VL5-VH4-Fc, VH4-VL5-VL6-VH6-VH5- VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-Fc, VL4-L7-VH5 -L8-VL6-L9-VH6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VH6-L9-VL6-L1 0-VH5-L11-VH4-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-Fc,VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VH6-L 9-VL6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-L12-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L 11-VL4-L12-Fc, VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc, or VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-L12-Fc. In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VL3-VH3-VH2-VL1-Fc, and the second polypeptide has a structure represented by Fc, VL4-VH4-Fc, VH4-VL4-Fc, VL4-L7-VH4-Fc, VL4-L7-VH4-L8-Fc, VH4-L7-VL4-Fc, VH4-L7-VL4-L8-Fc, VL4-VL5-VH5-VH4-Fc, VH4-VH5-VL5-VL4-Fc, VL4-L7-VL5-L8-VH5-L9-VH4-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-Fc, VH4-L7-VL ... H5-L9-VH4-L10-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-L10-Fc, VL4-VL5-VL6-VH6-V H5-VH4-Fc, VH4-VH5-VH6-VL6-VL5-VL4-Fc, VL4-VH5-VL6-VH6-VL5-VH4-Fc, VH 4-VL5-VH6-VL6-VH5-VL4-Fc, VL4-VL5-VH6-VL6-VH5-VH4-Fc, VH4-VH5-VL6-VH 6-VL5-VL4-Fc, VL4-VH5-VH6-VL6-VL5-VH4-Fc, VH4-VL5-VL6-VH6-VH5-VL4-Fc,VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-Fc, VL4-L7 -VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L 8-VH6-L9-VL6-L10-VH5-L11-VH4-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-Fc, VL4-L7-VH5-L8-VH6- L9-VL6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6 -L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VL6-L9-V H6-L10-VL5-L11-VH4-L12-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-L12-Fc, VL4-L7-VL5-L8-VH6-L9 -VL6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc, or VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-L12-Fc. In some embodiments, the first polypeptide has a structure represented by VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-Fc, and the second polypeptide has a structure represented by Fc, VL4-VH4-Fc, VH4-VL4-Fc, VL4-L7-VH4-Fc, VL4-L7-VH4-L8-Fc, VH4-L7-VL4-Fc, VH4-L7-VL4-L8-Fc, VL4-VL5-VH5-VH4-Fc, VH4-VH5-VL5-VL4-Fc, VL4-L7-VL5-L8-VH5-L9-VH4-Fc,VH4-L7-VH5-L8-VL5-L9-VL4-Fc, L7-VL5-L8-VH5-L9-VH4-L10-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-L10-Fc, VL4-VL5-VL6-VH6-VH5-VH4-Fc, VH4-VH5-V H6-VL6-VL5-VL4-Fc、VL4-VH5-VL6-VH6-VL5-VH4-Fc、VH4-VL5-VH6-VL6-V H5-VL4-Fc、VL4-VL5-VH6-VL6-VH5-VH4-Fc、VH4-VH5-VL6-VH6-VL5-VL4-F c、VL4-VH5-VH6-VL6-VL5-VH4-Fc、VH4-VL5-VL6-VH6-VH5-VL4-Fc、VL4-L7 -VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-Fc、VH4-L7-VH5-L8-VH6-L9-VL6 -L10-VL5-L11-VL4-Fc、VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-Fc、VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-Fc、VL4-L7-VL5-L8-VH 6-L9-VL6-L10-VH5-L11-VH4-Fc、VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L 11-VL4-Fc、VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-Fc、VH4-L7-V L5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4 -L12-Fc、VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-L12-Fc、VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-L12-Fc、VL4-L7-VL5-L8-VH6-L9 -VL6-L10-VH5-L11-VH4-L12-Fc、VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-L12-Fc、VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc、or has a structure represented by VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-L12-Fc. In some embodiments, the first polypeptide has a structure represented by VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-Fc, and the second polypeptide has a structure represented by VL4-VH4-Fc, VH4-VL4-Fc, VL4-L7-VH4-Fc, VL4-L7-VH4-L8-Fc, VH4-L7-VL4-Fc, VH4-L7-VL4-L8-Fc, VL4-VL5-VH5-VH4-Fc, VH4-VH5-VL5-VL4-Fc, VL4-L7-VL 5-L8-VH5-L9-VH4-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-Fc, L7-VL5-L8-VH5-L9-VH4-L10-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-L10-Fc, VL4-V L5-VL6-VH6-VH5-VH4-Fc, VH4-VH5-VH6-VL6-VL5-VL4-Fc, VL4-VH5-VL6-VH6-VL5-VH4-Fc, VH4-VL5-VH6-VL6-VH5-VL4-Fc, VL4-VL5-VH 6-VL6-VH5-VH4-Fc, VH4-VH5-VL6-VH6-VL5-VL4-Fc, VL4-VH5-VH6-VL6-VL5-VH4-Fc, VH4-VL5-VL6-VH6-VH5-VL4-Fc, VL4-L7-VL5-L8- VL6-L9-VH6-L10-VH5-L11-VH4-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-Fc, VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH 4-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-Fc, VH4-L7-VH5-L8-VL6-L 9-VH6-L10-VL5-L11-VL4-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-Fc,VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-L12-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-L12-Fc, VL4-L7- VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc, or VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-L12-Fc. In some embodiments, the first polypeptide has a structure represented by VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-Fc, and the second polypeptide has a structure represented by Fc, VL4-VH4-Fc, VH4-VL4-Fc, VL4-L7-VH4-Fc, VL4-L7-VH4-L8-Fc, VH4-L7-VL4-Fc, VH4-L7-VL4-L8-Fc, VL4-VL5-VH5-VH4-Fc c, VH4-VH5-VL5-VL4-Fc, VL4-L7-VL5-L8-VH5-L9-VH4-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-Fc, L7-VL5-L8-VH5-L9-V H4-L10-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-L10-Fc, VL4-VL5-VL6-VH6-VH5-VH4-Fc, VH4-VH5-VH6-VL6-VL5-VL4-Fc, VL4-VH5-VL6-VH6-VL5-VH4-Fc, VH4-VL5-VH6-VL6-VH5-VL4-Fc, VL4-VL5-VH6-VL6-VH5-VH4-Fc, VH4-VH5-VL6-VH 6-VL5-VL4-Fc, VL4-VH5-VH6-VL6-VL5-VH4-Fc, VH4-VL5-VL6-VH6-VH5-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10- VH5-L11-VH4-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-Fc, VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11 -VH4-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-Fc,VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-Fc, VL4-L7-VH5-L8-VH6-L9-V L6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-Fc, V L4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VH6-L 9-VL6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-V H4-L12-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-L12-Fc, VL4-L7-V L5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L1 0-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc, or VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-L12-Fc. In some embodiments, the first polypeptide has a structure represented by VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-Fc, and the second polypeptide has a structure represented by Fc, VL4-VH4-Fc, VH4-VL4-Fc, VL4-L7-VH4-Fc, VL4-L7-VH4-L8-Fc, VH4-L7-VL4-Fc, VH4-L7-VL4-L8-Fc, VL4-VL5-VH5-VH4-Fc, VH4-VH5-VL5-VL4-Fc, VL4-L7-VL5-L8-VH5- L9-VH4-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-Fc, L7-VL5-L8-VH5-L9-VH4-L10-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-L10-Fc, VL4-VL5-VL6-VH6-VH 5-VH4-Fc, VH4-VH5-VH6-VL6-VL5-VL4-Fc, VL4-VH5-VL6-VH6-VL5-VH 4-Fc, VH4-VL5-VH6-VL6-VH5-VL4-Fc, VL4-VL5-VH6-VL6-VH5-VH4-Fc,VH4-VH5-VL6-VH6-VL5-VL4-Fc, VL4-VH5-VH6-VL6-VL5-VH4-Fc, VH4-VL5-VL6-VH6-VH5-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH 6-L10-VH5-L11-VH4-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-Fc, VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH 4-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-Fc, VH4-L7-VH5- L8-VL6-L9-VH6-L10-VL5-L11-VL4-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VL6-L9-VH6-L10 -VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4 -L12-Fc, VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-L12-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-L12-Fc, VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc, or VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-L12-Fc. In some embodiments, the first polypeptide has a structure represented by VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-Fc, and the second polypeptide has a structure represented by Fc, VL4-VH4-Fc, VH4-VL4-Fc, VL4-L7-VH4-Fc, VL4-L7-VH4-L8-Fc, VH4-L7-VL4-Fc,VH4-L7-VL4-L8-Fc, VL4-VL5-VH5-VH4-Fc, VH4-VH5-VL5-VL4-Fc, VL4-L7-VL5-L8-VH5-L9-VH4-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-Fc, L7-VL5-L8-VH5-L9-VL4-Fc, VH4-L7-VH5-L8-VLL10-Fc, VL4-VL5-VL6-VH6-VH5-VH4-Fc, VH4-VH5-VH6-VL6-VL5-VL4-Fc, VL4-VH5-VH6-VL6-VL5-VL4-Fc, VL4-VH5-VH6-VL6-VL5-VL4-Fc, VL4-VH5-VH6-VL6-VL5-VL4-Fc -VH4-Fc, VH4-VL5-VH6-VL6-VH5-VL4-Fc, VL4-VL5-VH6-VL6-VH5-VH4-Fc, VH4-VH5-VL6-VH6-VL5-VL4-Fc, VL4-VH5-VH6-VL6-VL5-VL4-Fc, VL4-VH5-VH6-VL6-VL5-VH4-Fc, VH4-VL5-VL6-VH6-VH5-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-Fc, VL4-L7-VH5-L8-VH6-L9-VL VL6-L9-VH6-L10-VL5-L11-VH4-Fc、VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-Fc、VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-Fc、VH4- L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-Fc、VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-Fc、VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL 4-Fc、VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-L12-Fc、VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-L12-Fc、VL4-L7-VH5-L8-VL6-L9- VH6-L10-VL5-L11-VH4-L12-Fc、VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-L12-Fc、VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-L12-Fc、and VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc, or VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-L12-Fc. In some embodiments, the first polypeptide has a structure represented by VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-Fc, and the second polypeptide has a structure represented by Fc, VL4-VH4-Fc, VH4-VL4-Fc, VL4-L7-VH4-Fc, VL4-L7-VH4-L8-Fc, VH4-L7-VL4-Fc, VH4-L7-VL4-L8-Fc, VL4-VL5-VH5-VH4-Fc, VH4-VH 5-VL5-VL4-Fc, VL4-L7-VL5-L8-VH5-L9-VH4-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-Fc, L7-VL5-L8-VH5-L9-VH4-L10-Fc, VH4- L7-VH5-L8-VL5-L9-VL4-L10-Fc, VL4-VL5-VL6-VH6-VH5-VH4-Fc, VH4-VH5-VH6-VL6-VL5-VL4-Fc, VL4-VH5-VL6-VH6-VL5- VH4-Fc, VH4-VL5-VH6-VL6-VH5-VL4-Fc, VL4-VL5-VH6-VL6-VH5-VH4-Fc, VH4-VH5-VL6-VH6-VL5-VL4-Fc, VL4-VH5-VH6-V L6-VL5-VH4-Fc, VH4-VL5-VL6-VH6-VH5-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-Fc, VH4-L7-VH5-L8-VH6 -L9-VL6-L10-VL5-L11-VL4-Fc, VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-V H5-L11-VL4-Fc, VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-Fc,VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VL6-L9-VH6-L10-V L5-L11-VH4-L12-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-L12-Fc, VL 4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VL6-L9-VH VH4-L7-VL5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-L12-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc, or VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-L12-Fc. In some embodiments, the first polypeptide has a structure represented by VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-Fc, and the second polypeptide has a structure represented by VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-Fc, VH4-VL4-Fc, VH4-VL4-Fc, VL4-L7-VH4-Fc, VL4-L7-VH4-L8-Fc, VH4-L7-VL4-Fc, VH4-L7-VL4-L8-Fc, VL4-VL 5-VH5-VH4-Fc, VH4-VH5-VL5-VL4-Fc, VL4-L7-VL5-L8-VH5-L9-VH4-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-Fc, L7 -VL5-L8-VH5-L9-VH4-L10-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-L10-Fc, VL4-VL5-VL6-VH6-VH5-VH4-Fc, VH4-V H5-VH6-VL6-VL5-VL4-Fc, VL4-VH5-VL6-VH6-VL5-VH4-Fc, VH4-VL5-VH6-VL6-VH5-VL4-Fc, VL4-VL5-VH6-VL 6-VH5-VH4-Fc, VH4-VH5-VL6-VH6-VL5-VL4-Fc, VL4-VH5-VH6-VL6-VL5-VH4-Fc, VH4-VL5-VL6-VH6-VH5-VL4 -Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-F c, VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-Fc,VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L10 -VL5-L11-VL4-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L 8-VL6-L9-VH6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4 -L12-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VL 6-L9-VH6-L10-VL5-L11-VH4-L12-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4 -L12-Fc, VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VL VH4-L7-VL5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc, or VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-L12-Fc. In some embodiments, the first polypeptide has a structure represented by VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-Fc, and the second polypeptide has a structure represented by VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-Fc, VH4-VL4-Fc, VH4-VL4-Fc, VL4-L7-VH4-Fc, VL4-L7-VH4-L8-Fc, VH4-L7-VL4-Fc, VH4-L7-VL4-L8-Fc, VL4-VL5-VH5-VH4-Fc, VH4-VH5-VL 5-VL4-Fc, VL4-L7-VL5-L8-VH5-L9-VH4-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-Fc, L7-VL5-L8-VH5-L9-VH4-L10-Fc, VH4-L7-VH5 -L8-VL5-L9-VL4-L10-Fc, VL4-VL5-VL6-VH6-VH5-VH4-Fc, VH4-VH5-VH6-VL6-VL5-VL4-Fc, VL4-VH5-VL6-VH6-VL5-VH4-Fc,VH4-VL5-VH6-VL6-VH5-VL4-Fc, VL4-VL5-VH6-VL6-VH5-VH4-Fc, VH4-VH5-VL6-VH6-VL5-VL4-Fc, VL4-VH5-VH6-VL6-VL5-VH4-Fc, VH4 -VL5-VL6-VH6-VH5-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-Fc , VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VH6-L9-V L6-L10-VH5-L11-VH4-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-Fc, V H4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VH6-L9 -VL6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-L12-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L1 1-VL4-L12-Fc, VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc, or VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-L12-Fc. In some embodiments, the first polypeptide has a structure represented by VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-Fc, and the second polypeptide has a structure represented by Fc, VL4-VH4-Fc, VH4-VL4-Fc,VL4-L7-VH4-Fc, VL4-L7-VH4-L8-Fc, VH4-L7-VL4-Fc, VH4-L7-VL4-L8-Fc, VL4-VL5-VH5-VH4-Fc, VH4-VH5-VL5-VL4-Fc, VL4-L7-VL5-L8-VH5-L9-VH4-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-Fc, L7-VL5-L8-VH5-L9-VL4-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-Fc, V H4-VH5-VH6-VL6-VL5-VL4-Fc、VL4-VH5-VL6-VH6-VL5-VH4-Fc、VH4-VL5-VH6-VL6-VH5-VL4-Fc、VL4-VL5-VH6-VL6-VH5-VH4-Fc、VH4-VH5-VL6-VH6 -VL5-VL4-Fc、VL4-VH5-VH6-VL6-VL5-VH4-Fc、VH4-VL5-VL6-VH6-VH5-VL4-Fc、VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-Fc、VH4-L7-VH5-L 8-VH6-L9-VL6-L10-VL5-L11-VL4-Fc、VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-Fc、VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-Fc、VL 4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-Fc、VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-Fc、VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11 -VH4-Fc、VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-Fc、VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-L12-Fc、VH4-L7-VH5-L8-VH6-L9-V L6-L10-VL5-L11-VL4-L12-Fc、VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-L12-Fc、VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-L12-Fc、VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc, or VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-L12-Fc. In some embodiments, the first polypeptide has a structure represented by VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-Fc, and the second polypeptide has a structure represented by Fc, VL4-VH4-Fc, VH4-VL4-Fc, VL4-L7-VH4-Fc, VL4-L7-VH4-L8-Fc, VH4-L7-VL4-Fc, VH4-L7-VL4-L8-Fc, VL4-VL5-VH5-VH 4-Fc, VH4-VH5-VL5-VL4-Fc, VL4-L7-VL5-L8-VH5-L9-VH4-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-Fc, L7-VL5-L8-VH5-L9 -VH4-L10-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-L10-Fc, VL4-VL5-VL6-VH6-VH5-VH4-Fc, VH4-VH5-VH6-VL6-VL5-VL4-F c, VL4-VH5-VL6-VH6-VL5-VH4-Fc, VH4-VL5-VH6-VL6-VH5-VL4-Fc, VL4-VL5-VH6-VL6-VH5-VH4-Fc, VH4-VH5-VL6-V H6-VL5-VL4-Fc, VL4-VH5-VH6-VL6-VL5-VH4-Fc, VH4-VL5-VL6-VH6-VH5-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10 -VH5-L11-VH4-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-Fc, VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11 -VH4-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-Fc,VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-L12-Fc, VH4-L 7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-L12 -Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-L12-Fc, VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L1 1-VH4-L12-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc, or VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-L12-Fc. In some embodiments, the first polypeptide has a structure represented by VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-Fc, and the second polypeptide has a structure represented by VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-Fc, VH4-VL4-Fc, VH4-VL4-Fc, VL4-L7-VH4-Fc, VL4-L7-VH4-L8-Fc, VH4-L7-VL4 ... H4-L7-VL4-L8-Fc, VL4-VL5-VH5-VH4-Fc, VH4-VH5-VL5-VL4-Fc, VL4-L7-VL5-L8-VH5-L9-VH4- Fc, VH4-L7-VH5-L8-VL5-L9-VL4-Fc, L7-VL5-L8-VH5-L9-VH4-L10-Fc, VH4-L7-VH5-L8-VL5-L9 -VL4-L10-Fc, VL4-VL5-VL6-VH6-VH5-VH4-Fc, VH4-VH5-VH6-VL6-VL5-VL4-Fc, VL4-VH5-VL6-V H6-VL5-VH4-Fc, VH4-VL5-VH6-VL6-VH5-VL4-Fc, VL4-VL5-VH6-VL6-VH5-VH4-Fc, VH4-VH5-VL6 -VH6-VL5-VL4-Fc, VL4-VH5-VH6-VL6-VL5-VH4-Fc, VH4-VL5-VL6-VH6-VH5-VL4-Fc, VL4-L7-VL 5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-Fc,VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL 4-Fc, VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L 11-VL4-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VL6-L9-VH6-L10- VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VH6-L9 -VL6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-L12-Fc, VH4-L7- VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-L12-Fc, VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-L 12-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc, or VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-L12-Fc. In some embodiments, the first polypeptide has a structure represented by VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-Fc, and the second polypeptide has a structure represented by VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-Fc, VH4-VH4-Fc, VH4-VL4-Fc, VL4-L7-VH4-Fc, VL4-L7-VH4-L8-Fc, VH4-L7-VL4-Fc, VH4-L 7-VL4-L8-Fc, VL4-VL5-VH5-VH4-Fc, VH4-VH5-VL5-VL4-Fc, VL4-L7-VL5-L8-VH5-L9-VH4-Fc, VH4-L 7-VH5-L8-VL5-L9-VL4-Fc, L7-VL5-L8-VH5-L9-VH4-L10-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-L10-Fc,VL4-VL5-VL6-VH6-VH5-VH4-Fc, VH4-VH5-VH6-VL6-VL5-VL4-Fc, VL4-VH 5-VL6-VH6-VL5-VH4-Fc, VH4-VL5-VH6-VL6-VH5-VL4-Fc, VL4-VL5-VH6-V L6-VH5-VH4-Fc, VH4-VH5-VL6-VH6-VL5-VL4-Fc, VL4-VH5-VH6-VL6-VL5 -VH4-Fc, VH4-VL5-VL6-VH6-VH5-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L 10-VH5-L11-VH4-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-F c, VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-V H6-L9-VL6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH 5-L11-VH4-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-Fc, VL4- L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VL6-L9 -VH6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11- VH4-L12-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-L12-Fc, V L4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-L12-Fc, VH4-L7-VL5-L8- In some embodiments, the first polypeptide has a structure represented by: VH6-L9-VL6-L10-VH5-L11-VL4-L12-Fc, VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc, or VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-L12-Fc.It has the structure represented by VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-Fc, the 2nd polypeptide is Fc, VL4-VH4-Fc, VH4-VL4-Fc, VL4-L7-VH4-Fc, VL4-L7-VH4-L8-Fc. 、VH4-L7-VL4-Fc、VH4-L7-VL4-L8-Fc、VL4-VL5-VH5-VH4-Fc、VH4-VH5-VL5-VL4-Fc、VL4-L7-VL5-L8-VH5-L9-VH4-Fc、VH4-L7-VH5-L8-VL5-L9-VL 4-Fc, L7-VL5-L8-VH5-L9-VH4-L10-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-L10-Fc, VL4-VL5-VL6-VH6-VH5-VH4-Fc, VH4-VH5-VH6-VL6-VL5-VL4-Fc, VL4-VH5-VL6-VH6-VL5-VL4-Fc, VL4-VH5-VL6-VH6-VL5-VL4-Fc, VH4-VL5-VH6-VL6-VL4-Fc, VL4-VL5-VH6-VL6-VL4-Fc, VL4-VL5-VH6-VL6-VL5-VL4-Fc, VL4-VL5-VH6-VL6-VL4-Fc, VL4-VL5-VH6-VL6-VL5-VH VL5-VH4-Fc、VH4-VL5-VL6-VH6-VH5-VL4-Fc、VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-Fc、VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL 4-Fc、VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-Fc、VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-Fc、VL4-L7-VL5-L8-VH6-L9-VL6-L10- VH5-L11-VH4-Fc、VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-Fc、VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-Fc、VH4-L7-VL5-L8-VL6 L9-VH6-L10-VH5-L11-VL4-Fc、VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-L12-Fc、VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-L12-Fc、VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-L12-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10 -VH5-L11-VL4-L12-Fc, VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-V H5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc, or VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-L12-Fc. In some embodiments, the first polypeptide has a structure represented by VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-Fc, and the second polypeptide has a structure represented by VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-Fc, VL4-VH4-Fc, VH4-VL4-Fc, VL4-L7-VH4-Fc, VL4-L7-VH4-L8-Fc, VH4-L7-VL4-Fc, VH4-L7-VL4-Fc, VH4-L7-VL 4-L8-Fc, VL4-VL5-VH5-VH4-Fc, VH4-VH5-VL5-VL4-Fc, VL4-L7-VL5-L8-VH5-L9-VH4-Fc, VH4-L7-VH5- L8-VL5-L9-VL4-Fc, L7-VL5-L8-VH5-L9-VH4-L10-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-L10-Fc, VL4-VL5- VL6-VH6-VH5-VH4-Fc, VH4-VH5-VH6-VL6-VL5-VL4-Fc, VL4-VH5-VL6-VH6-VL5-VH4-Fc, VH4-VL5-VH6- VL6-VH5-VL4-Fc, VL4-VL5-VH6-VL6-VH5-VH4-Fc, VH4-VH5-VL6-VH6-VL5-VL4-Fc, VL4-VH5-VH6-VL6- VL5-VH4-Fc, VH4-VL5-VL6-VH6-VH5-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-Fc, VH4 -L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-Fc, VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-Fc,VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-Fc、VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-Fc、VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-Fc、VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-Fc、VH4-L7-VL5-L8-VL6-L9-VH6、 -L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11- VL4-L12-Fc, VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-L12-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-L12-F c, VL4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc, or VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-L12-Fc. In some embodiments, the first polypeptide has a structure represented by VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-Fc, and the second polypeptide has a structure represented by Fc, VL4-VH4-Fc, VH4-VL4-Fc, VL4-L7-VH4-Fc, VL4-L7-VH4 -L8-Fc, VH4-L7-VL4-Fc, VH4-L7-VL4-L8-Fc, VL4-VL5-VH5-VH4-Fc, VH4-VH5-VL5 -VL4-Fc, VL4-L7-VL5-L8-VH5-L9-VH4-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-Fc, L7-V L5-L8-VH5-L9-VH4-L10-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-L10-Fc, VL4-VL5-VL6- VH6-VH5-VH4-Fc, VH4-VH5-VH6-VL6-VL5-VL4-Fc, VL4-VH5-VL6-VH6-VL5-VH4-Fc , VH4-VL5-VH6-VL6-VH5-VL4-Fc, VL4-VL5-VH6-VL6-VH5-VH4-Fc, VH4-VH5-VL6-V H6-VL5-VL4-Fc, VL4-VH5-VH6-VL6-VL5-VH4-Fc, VH4-VL5-VL6-VH6-VH5-VL4-Fc,VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-Fc, VL4-L7 -VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L 8-VH6-L9-VL6-L10-VH5-L11-VH4-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-Fc, VL4-L7-VH5-L8-VH6- L9-VL6-L10-VL5-L11-VH4-Fc, VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6 -L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VL6-L9-V H6-L10-VL5-L11-VH4-L12-Fc, VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-L12-Fc, VL4-L7-VL5-L8-VH6-L9 -VL6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-L12-Fc, VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc, or VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-L12-Fc. In some embodiments, the first polypeptide has a structure represented by VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-Fc, and the second polypeptide has a structure represented by Fc, VL4-VH4-Fc, VH4-VL4-Fc, VL4-L7-VH4-Fc, VL4-L7-VH4-L8-Fc, VH4-L7-VL4-Fc, VH4-L7-VL4-L8-Fc, VL4-VL5-VH5-VH4-Fc, VH4-VH5-VL5-VL4-Fc, VL4-L7-VL5-L8-VH5-L9-VH4-Fc,VH4-L7-VH5-L8-VL5-L9-VL4-Fc, L7-VL5-L8-VH5-L9-VH4-L10-Fc, VH4-L7-VH5-L8-VL5-L9-VL4-L10-Fc, VL4-VL5-VL6-VH6-VH5-VH4-Fc, VH4-VH5-V H6-VL6-VL5-VL4-Fc、VL4-VH5-VL6-VH6-VL5-VH4-Fc、VH4-VL5-VH6-VL6-V H5-VL4-Fc、VL4-VL5-VH6-VL6-VH5-VH4-Fc、VH4-VH5-VL6-VH6-VL5-VL4-F c、VL4-VH5-VH6-VL6-VL5-VH4-Fc、VH4-VL5-VL6-VH6-VH5-VL4-Fc、VL4-L7 -VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-Fc、VH4-L7-VH5-L8-VH6-L9-VL6 -L10-VL5-L11-VL4-Fc、VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-Fc、VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-Fc、VL4-L7-VL5-L8-VH 6-L9-VL6-L10-VH5-L11-VH4-Fc、VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L 11-VL4-Fc、VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-Fc、VH4-L7-V L5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-Fc, VL4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VH4-L12-Fc, VH4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VL4 -L12-Fc、VL4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VH4-L12-Fc、VH4-L7-VL5-L8-VH6-L9-VL6-L10-VH5-L11-VL4-L12-Fc、VL4-L7-VL5-L8-VH6-L9 -VL6-L10-VH5-L11-VH4-L12-Fc、VH4-L7-VH5-L8-VL6-L9-VH6-L10-VL5-L11-VL4-L12-Fc、VL4-L7-VH5-L8-VH6-L9-VL6-L10-VL5-L11-VH4-L12-Fc、or VH4-L7-VL5-L8-VL6-L9-VH6-L10-VH5-L11-VL4-L12-Fc.

[0083] In some aspects, the antigen-binding polypeptide further comprises at least one CH1 region and / or CL region, optionally located at its carboxy terminus. For example, the carboxy terminus of the polypeptide may comprise a CH1 region. For example, the carboxy terminus of the polypeptide may comprise a CL region. For example, the carboxy terminus of the polypeptide may comprise both a CH1 and a CL region. In some aspects, the carboxy terminus of the polypeptide comprises the structure CH1-CL. In some aspects, the carboxy terminus of the polypeptide comprises the structure CL-CH1. The CH1 region and / or CL region may be linked to the polypeptide via one or more amino acid linkers. When both a CH1 region and a CL region are present, they may be linked to each other via one or more amino acid linkers. For example, the antigen-binding polypeptide can be VL1-VL2-VL3-VH3-VH2-VH1-CH1-CL, VL1-VL2-VL3-VH3-VH2-VH1-CL-CH1, VH1-VH2-VH3-VL3-VL2-VL1-CH1-CL, VH1-VH2-VH3-VL3-VL2-VL1-CL-CH1, VH1-VH2-VH3-VL3-VL2-VL1-CL-CH1, VL1-VH2-VL3-VH3-VL2-VL1-CL-CH1, VL1-VH2-VL3 -VH3-VL2-VH1-CH1-CL, VL1-VH2-VL3-VH3-VL2-VH1-CL-CH1, VH1-VL2-VH3-VL3-VH2-VL1-C H1-CL, VH1-VL2-VH3-VL3-VH2-VL1-CL-CH1, VL1-VL2-VH3-VL3-VH2-VH1-CH1-CL, VL1-VL2- VH3-VL3-VH2-VH1-CL-CH1, VH1-VH2-VL3-VH3-VL2-VL1-CH1-CL, VH1-VH2-VL3-VH3-VL2-VL 1-CL-CH1, VL1-VH2-VH3-VL3-VL2-VH1-CH1-CL, VL1-VH2-VH3-VL3-VL2-VH1-CL-CH1, VH1-V L2-VL3-VH3-VH2-VL1-CH1-CL, VH1-VL2-VL3-VH3-VH2-VL1-CL-CH1, VL1-L1-VL2-L2-VL3-L 3-VH3-L4-VH2-L5-VH1-CH1-CL, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CH1-CL,VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CH1-L7-CL, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CL-CH1, VL1-L1-VL2-L2-VL3-L3-VH3 -L4-VH2-L5-VH1-L6-CL-CH1, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CL-L7-CH1, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CH1-CL, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CH1-L7-CL, VH1-L1-VH2-L2-VH3-L3- VL3-L4-VL2-L5-VL1-CL-CH1, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CL-CH1, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CL-L7-CH1, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CH1-CL, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CH1-CL, VL1-L1-VH2-L2-VL3-L3-VH3 -L4-VL2-L5-VH1-L6-CH1-L7-CL、VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CL-CH1、VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CL-CH1、VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CL-L7-CH1、VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CH1-CL、VH1-L1-VL2-L2-VH3-L3-VL3 -L4-VH2-L5-VL1-L6-CH1-CL、VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CH1-L7-CL、VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CL-CH1、VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CL-CH1, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CL-L7-CH1, VL1-L1-VL2-L2-VH3-L3- VL3-L4-VH2-L5-VH1-CH1-CL, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CH1-CL, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CH1-L7- CL, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CL-CH1, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CL-CH1, VL1-L1-VL2-L2-VH3-L3-VL3- L4-VH2-L5-VH1-L6-CL-L7-CH1, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CH1-CL, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CH1-CL, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CH1-L7-CL, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CL-CH1, VH1-L1-VH2-L2-VL3-L3-VH3-L 4-VL2-L5-VL1-L6-CL-CH1, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CL-L7-CH1, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CH1-CL, VL 1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CH1-CL、VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CH1-L7-CL、VL1-L1-VH2-L2-VH3-L3-VL3 -L4-VL2-L5-VH1-CL-CH1、VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CL-CH1、VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CL-L7-CH1、VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CH1-CL, VH1-L1-VL2-L2-VL3-L3-V H3-L4-VH2-L5-VL1-L6-CH1-CL, VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6 -CH1-L7-CL, VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CL-CH1, VH1-L1-VL2- L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CL-CH1, or VH1-L1-VL2-L2-VL3-L3-VH3-L4 -VH2-L5-VL1-L6-CL-L7-CH1, where VL1 is a first immunoglobulin light chain variable region, VL2 is a second immunoglobulin light chain variable region, VL3 is a third immunoglobulin light chain variable region, VH1 is a first immunoglobulin heavy chain variable region, VH2 is a second immunoglobulin heavy chain variable region, VH3 is a third immunoglobulin heavy chain variable region, CH1 is immunoglobulin heavy chain constant region 1, CL is an immunoglobulin light chain constant region, and L1, L2, L3, L4, L5, L6, and L7 are amino acid linkers.

[0084] In some aspects, the antigen-binding polypeptide complex defined herein further comprises at least one CH1 region and / or CL region, optionally located at the carboxy terminus of the first polypeptide and / or second polypeptide. For example, the carboxy terminus of the first polypeptide and / or second polypeptide may comprise a CH1 region. For example, the carboxy terminus of the first polypeptide and / or second polypeptide may comprise a CL region. For example, the carboxy terminus of the first polypeptide and / or second polypeptide may comprise both a CH1 and a CL region. In some aspects, the carboxy terminus of the first polypeptide and / or second polypeptide comprises the structure CH1-CL. In some aspects, the carboxy terminus of the first polypeptide and / or second polypeptide comprises the structure CL-CH1. The CH1 region and / or CL region may be linked to the first polypeptide and / or second polypeptide via one or more amino acid linkers. When both a CH1 region and a CL region are present, they may be linked to each other via one or more amino acid linkers. For example, an antigen-binding complex can comprise a first polypeptide and a second polypeptide, wherein the first polypeptide has the sequence VL1-VL2-VL3-VH3-VH2-VH1-CH1, VL1-VL2-VL3-VH3-VH2-VH1-CL, VL1-VL2-VL3-VH3-VH2-VH1-CH1-CL, VL1-VL2-VL3-VH3-VH2-VH1-CL-CH1, VH1-VH2-VH3-VL3-VL2-VL1-CH1, VH1-VH2-VH3-VL3-VL2-VL1-CL, VH1-VH2-VH3-VL3-VL2-VL1-CL, VH1-VH2-VH3-VL3-VL2-VL1-CL, VH1-VH2-VH3-VL3-VL2-VL1-CH1, VH1-VH2-VH3-VL3-VL2-VL1-CL, VH1-VH2-VH3-VL3-VL2-VL 1-CH1-CL, VH1-VH2-VH3-VL3-VL2-VL1-CL-CH1, VL1-VH2-VL3-VH3-VL2-VH1-CH1, VL1-VH2-VL3-VH3-VL2-VH1-CL, VL1-VH2-VL3-VH3-VL2-VH1-CH 1-CL, VL1-VH2-VL3-VH3-VL2-VH1-CL-CH1, VH1-VL2-VH3-VL3-VH2-VL1-CH1, VH1-VL2-VH3-VL3-VH2-VL1-CL, VH1-VL2-VH3-VL3-VH2-VL1-CH1-CL,VH1-VL2-VH3-VL3-VH2-VL1-CL-CH1、VL1-VL2-VH3-VL3-VH2-VH1-CH1、V L1-VL2-VH3-VL3-VH2-VH1-CL、VL1-VL2-VH3-VL3-VH2-VH1-CH1-CL、VL1- VL2-VH3-VL3-VH2-VH1-CL-CH1、VH1-VH2-VL3-VH3-VL2-VL1-CH1、VH1-V H2-VL3-VH3-VL2-VL1-CL、VH1-VH2-VL3-VH3-VL2-VL1-CH1-CL、VH1-VH2- VL3-VH3-VL2-VL1-CL-CH1、VL1-VH2-VH3-VL3-VL2-VH1-CH1、VL1-VH2-V H3-VL3-VL2-VH1-CL、VL1-VH2-VH3-VL3-VL2-VH1-CH1-CL、VL1-VH2-VH3- VL3-VL2-VH1-CL-CH1, VH1-VL2-VL3-VH3-VH2-VL1-CH1, VH1-VL2-VL3-VH3-VH2-VL1-CL, VH1-VL2-VL3-VH3-VH2-VL1-CH1-CL, VH1-VL2-VL3-VH3-VH2-VL1-CL-CH1, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CH1, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CH1, VL1-L1-VL2-L2-VL3 -L3-VH3-L4-VH2-L5-VH1-CL、VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CL、VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CH1-CL、VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CH1-L7-CL、VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CH1-L7-CL、VL1-L1-VL2-L2-VL3-L3-VH3- L4-VH2-L5-VH1-CL-CH1, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CL-CH1, VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-L6-CL-L7-CH1VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CH1, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CH1, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L 5-VL1-CL、VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CL、VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CH1-CL、VH1-L1-VH2-L2-VH3-L3-VL 3-L4-VL2-L5-VL1-L6-CH1-CL、VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CH1-L7-CL、VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CL-CH1 VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CL-CH1, VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-L6-CL-L7-CH1, VL1-L1-VH2-L2-VL3-L3- VH3-L4-VL2-L5-VH1-CH1, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CH1, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CL, VL1-L1-VH2-L2 -VL3-L3-VH3-L4-VL2-L5-VH1-L6-CL、VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CH1-CL、VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CH1 -CL、VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CH1-L7-CL、VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CL-CH1、VL1-L1-VH2-L2-VL3-L3- VH3-L4-VL2-L5-VH1-L6-CL-CH1, VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-L6-CL-L7-CH1, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CH1VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CH1, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CL, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5- VL1-L6-CL, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CH1-CL, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CH1-CL, VH1-L1-VL2-L2-VH3- L3-VL3-L4-VH2-L5-VL1-L6-CH1-L7-CL、VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CL-CH1、VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-C L-CH1, VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-L6-CL-L7-CH1, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CH1, VL1-L1-VL2-L2-VH3-L3-VL 3-L4-VH2-L5-VH1-L6-CH1, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CL, VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CL, VL1-L1-VL2-L2 -VH3-L3-VL3-L4-VH2-L5-VH1-CH1-CL、VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CH1-CL、VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CH1-L7-CL、VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CL-CH1、VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-L6-CL-CH1、VL1-L1-VL2-L2-VH3 -L3-VL3-L4-VH2-L5-VH1-L6-CL-L7-CH1、VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CH1、VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CH1、VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CL、VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CL、VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5- VL1-CH1-CL, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CH1-CL, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CH1-L7-CL, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CL-CH1, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-L6-CL-CH1, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1- L6-CL-L7-CH1, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CH1, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CH1, VL1-L1-VH2-L2-VH3-L3- VL3-L4-VL2-L5-VH1-CL, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CL, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CH1-CL, VL1-L1-VH2 -L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CH1-CL、VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CH1-L7-CL、VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CL-CH1、VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CL-CH1、VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-L6-CL-L7-CH1、VH1-L1-V L2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CH1, VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CH1, VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CLVH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CL, VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CH1-CL, VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CH1-CL, VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CH1-L7-CL, VH1-L1-VL2-L2-VL3-L3-VH3-L4- VH2-L5-VL1-CL-CH1、VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CL-CH1、or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-L6-CL-L7-CH1 It has the structure shown by the 2nd polypeptide, VL4-VH4-CH1、VL4-VH4-CL、VL4-VH4-CH1-CL、VL4-VH4-CL-CH1、VH4-VL4-CH1、VH4-VL4-CL、VH4-VL4-CH1-CL、VH4-VL 4-CL-CH1、VL4-L8-VH4-CH1、VL4-L8-VH4-CL、VL4-L8-VH4-CH1-CL、VL4-L8-VH4-CL-CH1、VH4-L8-VL4-CH1、VH4-L8-VL4-CL、VH4-L8-VH4-CH1-CL、VH4-L8-VH4-CH1 H4-L8-VH4-CL-CH1、VL4-VL5-VH5-VH4-CH1、VL4-VL5-VH5-VH4-CL、VL4-VL5-VH5-VH4-CH1-CL、VL4-VL5-VH5-VH4-CL-CH1、VH4-VH5-VL5-VL4-CH1、 VH4-VH5-VL5-VL4-CL、VH4-VH5-VL5-VL4-CH1-CL、VH4-VH5-VL5-VL4-CL-CH1、VL4-L8-VL5-L9-VH5-L10-VH4-CH1、VL4-L8-VL5-L9-VH5-L10-VH4- CL、VL4-L8-VL5-L9-VH5-L10-VH4-CH1-CL、VL4-L8-VL5-L9-VH5-L10-VH4-CL-CH1、VH4-L8-VH5-L9-VL5-L10-VL4-CH1、VH4-L8-VH5-L9-VL5-L10-V L4-CL、VH4-L8-VH5-L9-VL5-L10-VL4-CH1-CL、VH4-L8-VH5-L9-VL5-L10-VL4-CL-CH1、VL4-VL5-VL6-VH6-VH5-VH4-CH1、VL4-VL5-VL6-VH6-VH5-VH 4-CL、VL4-VL5-VL6-VH6-VH5-VH4-CH1-CL、VL4-VL5-VL6-VH6-VH5-VH4-CL-CH1、VH4-VH5-VH6-VL6-VL5-VL4-CH1、VH4-VH5-VH6-VL6-VL5-VL4-CL、VH4-VH5-VH6-VL6-VL5-VL4-CH1-CL、VH4-VH5-VH6-VL6-VL5-VL4-CL-CH1、VL4-VH5-VL6-VH6-VL5-VH4-CH1、VL4-VH5-VL6-VH6-VL5-VH4-CL、VL4-VH5-VL6-VH6-VL5-VH4-CH1-CL、VL4-VH5-VL6-VH6-VL5-VH4-CL-CH1、VH4-VL5-VH6-VL6-VH5-VL4-CH1、VH4-VL5-VH6-VL6-VH5-VL4-CL、VH4-VL5-VH6-VL6-VH5-VL4-CH1-CL、VH4-VL5-VH6-VL6-VH5-VL4-CL-CH1、VL4-VL5-VH6-VL6-VH5-VH4-CH1、VL4-VL5-VH6-VL6-VH5-VH4-CL、VL4-VL5-VH6-VL6-VH5-VH4-CH1-CL、VL4-VL5-VH6-VL6-VH5-VH4-CL-CH1、VH4-VH5-VL6-VH6-VL5-VL4-CH1、VH4-VH5-VL6-VH6-VL5-VL4-CL、VH4-VH5-VL6-VH6-VL5-VL4-CH1-CL、VH4-VH5-VL6-VH6-VL5-VL4-CL-CH1、VL4-VH5-VH6-VL6-VL5-VH4-CH1、VL4-VH5-VH6-VL6-VL5-VH4-CL、VL4-VH5-VH6-VL6-VL5-VH4-CH1-CL、VL4-VH5-VH6-VL6-VL5-VH4-CL-CH1、VH4-VL5-VL6-VH6-VH5-VL4-CH1、VH4-VL5-VL6-VH6-VH5-VL4-CL、VH4-VL5-VL6-VH6-VH5-VL4-CH1-CL、VH4-VL5-VL6-VH6-VH5-VL4-CL-CH1、VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-CH1、VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-CL、VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-CH1-CL、VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-CL-CH1、VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-CH1、VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-CL、VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-CH1-CL、VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-CL-CH1、VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-CH1、VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-CL、VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-CH1-CL、VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-CL-CH1、VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-CH1、VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L11-VL4-CL、VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-CH1-CL、VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-CL-CH1、VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-L13-CH1、VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-L13-CL、VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-L13-CH1-CL、VL4-L8-VL5-L9-VL6-L10-VH6-L11-VH5-L12-VH4-L13-CL-CH1、VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-L13-CH1、VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-L13-CL、VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-L13-CH1-CL、VH4-L8-VH5-L9-VH6-L10-VL6-L11-VL5-L12-VL4-L13-CL-CH1、VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-L13-CH1、VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-L13-CL、VL4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VH4-L13-CH1-CL、VL4-L8-VH5-L9-VL6-L10- VH6-L11-VL5-L12-VH4-L13-CL-CH1、VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-L13-CH1、VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-L1 3-CL、VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-L13-CH1-CL、or VH4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VL4-L13-CL-CH1、VL4-L8-VL5 -L9-VH6-L10-VL6-L11-VH5-L12-VH4-CH1、VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-CL、VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-CH 1-CL、VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-CL-CH1、VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-CH1、VH4-L8-VH5-L9-VL6-L10-VH 6-L11-VL5-L12-VL4-CL、VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-CH1-CL、VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-CL-CH1、VL4-L8 -VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-L13-CH1、VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-L13-CL、VL4-L8-VL5-L9-VH6-L10-VL6-L11-V H5-L12-VH4-L13-CH1-CL、VL4-L8-VL5-L9-VH6-L10-VL6-L11-VH5-L12-VH4-L13-CL-CH1、VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-L13-CH1、VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-L13-CL, VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-L13-CH1-CL, or VH4-L8-VH5-L9-VL6-L10-VH6-L11-VL5-L12-VL4-L13-CL-CH1, wherein VL1 is a first immunoglobulin light chain variable region, VL2 is a second immunoglobulin light chain variable region, VL3 is a third immunoglobulin light chain variable region, VL4 is a fourth immunoglobulin light chain variable region, and VL5 is a fourth immunoglobulin light chain variable region. VH1 is a first immunoglobulin heavy chain variable region, VH2 is a second immunoglobulin heavy chain variable region, VH3 is a third immunoglobulin heavy chain variable region, VH4 is a fourth immunoglobulin heavy chain variable region, VH5 is a fifth immunoglobulin heavy chain variable region, VH6 is a sixth immunoglobulin heavy chain variable region, CH1 is heavy chain constant region 1, CL is a light chain constant region, and L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, and L13 are amino acid linkers. In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VL3-VH3-VH2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, In some embodiments, the first polypeptides have a structure represented by VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, and the first polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini. In some embodiments, the first polypeptides have a structure represented by VL1-VL2-VL3-VH3-VH2-VH1,the second polypeptide is VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, The antibody has a structure represented by H5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acids. In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VL3-VH3-VH2-VH1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VL4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4 The antibody has a structure represented by VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VL3-VH3-VH2-VH1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VL4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VH4-VH5-VL6-VH6-VL5-VL4 , VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VL3-VH3-VH2-VH1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VL5-VH6-VH6-VL6-VL5-VL4, VH4-VL5-VH6-VL6-VH5-VL4, VH4-VL5-VH6-VL6-VH5-VL4, VH4-VH5-VL6-VH6-VL ... L4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1 is linked to the carboxy terminus of the first and / or second polypeptide via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VL3-VH3-VH2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5 -VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6 -VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6- The polypeptide has a structure represented by VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and optionally, the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1, if present, is linked to the carboxy terminus of the first and / or second polypeptide via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VL3-VH3-VH2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VL6 H6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6- The polypeptide has a structure represented by VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1, if present, is linked to the carboxy terminus of the first and / or second polypeptide via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VL3-VH3-VH2-VH1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5 -VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and when CH1 and CL are present in both the first and / or second polypeptides, they are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VL3-VH3-VH2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5 -VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5- The polypeptide has a structure represented by VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each contain CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, CH1, CL, CH1-CL, or CL-CH1, if present, are linked to the carboxy termini of the first and / or second polypeptide via one or more amino acid linkers, and CH1 and CL, if present in both the first and / or second polypeptide, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VL3-VH3-VH2-VH1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VL4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VH4-VH5-VL6-VH6-VL5-VL4 , VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and CH1 and CL, if present in both the first and / or second polypeptides, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VL3-VH3-VH2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VL6 H6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6- In some embodiments, the first polypeptide has a structure represented by VH6-VH5-VL4, wherein the first and second polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1, if present, are linked to the carboxy termini of the first and / or second polypeptides via one or more amino acid linkers, and CH1 and CL, if both present in the first and / or second polypeptides, are linked to each other via one or more amino acid linkers. VH4-VH5-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VL6-VH6-VL5 -VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, Each of the polypeptides comprises a CH1, CL, CH1-CL, or CL-CH1 at its carboxy terminus, and VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, CH1, CL, CH1-CL, or CL-CH1, if present, is linked to the carboxy terminus of the first and / or second polypeptide via one or more amino acid linkers, and CH1 and CL, if present in both the first and / or second polypeptide, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VH3-VL3-VL2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, and each of the first polypeptides has a structure represented by VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini. In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VH3-VL3-VL2-VL1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VH6-VL6-VH5-VL4 -VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acids.In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VH3-VL3-VL2-VL1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4 The antibody has a structure represented by VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers. In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VH3-VL3-VL2-VL1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VH4-VH5-VL6-VH6-VL5-VL4 , VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VH3-VL3-VL2-VL1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VH4-VL5-VH6-VL6-VH5-VL4, VH4-VH5-VL6-VH6-VL ... L4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1 is linked to the carboxy terminus of the first and / or second polypeptide via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VH3-VL3-VL2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5 -VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6 -VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6- The polypeptide has a structure represented by VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and optionally, the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1, if present, is linked to the carboxy terminus of the first and / or second polypeptide via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VH3-VL3-VL2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VL6 H6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6- The polypeptide has a structure represented by VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1, if present, is linked to the carboxy terminus of the first and / or second polypeptide via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VH3-VL3-VL2-VL1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5 -VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and when CH1 and CL are present in both the first and / or second polypeptides, they are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VH3-VL3-VL2-VL1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL and VH4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1, if present, is joined by one or more amino acid linkers. The CH1 and CL are linked to the carboxy termini of the first and / or second polypeptides via a linker, and when both CH1 and CL are present in the first and / or second polypeptides, they are linked to each other via one or more amino acid linkers. In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VH3-VL3-VL2-VL1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VH4-VH5-VL6-VH6-VL5-VL4 , VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and CH1 and CL, if present in both the first and / or second polypeptides, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VH3-VL3-VL2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VL6 H6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6- The polypeptide has a structure represented by VH6-VH5-VL4, wherein the first and second polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1, if present, are linked to the carboxy termini of the first and / or second polypeptides via one or more amino acid linkers, and the CH1 and CL, if present in both the first and / or second polypeptides, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VH3-VL3-VL2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4; the first polypeptide and the second polypeptide each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini; VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers; VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers; CH1, CL, CH1-CL, or CL-CH1, if present, is linked to the carboxy termini of the first and / or second polypeptide via one or more amino acid linkers; and CH1 and CL, if present in both the first and / or second polypeptide, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VL3-VH3-VL2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, and each of the first polypeptides has a structure represented by VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini. In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VL3-VH3-VL2-VH1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VL4, VH4-VL5-VH6-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6 -VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acids.In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VL3-VH3-VL2-VH1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VL4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4 The antibody has a structure represented by VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers. In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VL3-VH3-VL2-VH1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VH4-VH5-VL6-VH6-VL5-VL4 , VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VL3-VH3-VL2-VH1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VL4, VH4-VL5-VH6-VL6-VH6-VL5-VL4, VH4-VL5-VH6-VL6-VH5-VL4, VH4-VH5-VL6-VH6-VL ... L4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1 is linked to the carboxy terminus of the first and / or second polypeptide via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VL3-VH3-VL2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5 -VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6 -VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6- The polypeptide has a structure represented by VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and optionally, the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1, if present, is linked to the carboxy terminus of the first and / or second polypeptide via one or more amino acid linkers. In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VL3-VH3-VL2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6- VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each have a structure represented by The polypeptides each comprise CH1, CL, CH1-CL, or CL-CH1, and VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers; VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers; and CH1, CL, CH1-CL, or CL-CH1, if present, is linked to the carboxy terminus of the first and / or second polypeptide via one or more amino acid linkers. In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VL3-VH3-VL2-VH1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5 -VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and when CH1 and CL are present in both the first and / or second polypeptides, they are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VL3-VH3-VL2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5 -VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5- The polypeptide has a structure represented by VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each contain CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, CH1, CL, CH1-CL, or CL-CH1, if present, are linked to the carboxy termini of the first and / or second polypeptide via one or more amino acid linkers, and CH1 and CL, if present in both the first and / or second polypeptide, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VL3-VH3-VL2-VH1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VH4-VH5-VL6-VH6-VL5-VL4 , VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and CH1 and CL, if present in both the first and / or second polypeptides, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VL3-VH3-VL2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VL6 H6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6- The polypeptide has a structure represented by VH6-VH5-VL4, wherein the first and second polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1, if present, are linked to the carboxy termini of the first and / or second polypeptides via one or more amino acid linkers, and the CH1 and CL, if present in both the first and / or second polypeptides, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VL3-VH3-VL2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4; the first polypeptide and the second polypeptide each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini; VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers; VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers; CH1, CL, CH1-CL, or CL-CH1, if present, is linked to the carboxy termini of the first and / or second polypeptide via one or more amino acid linkers; and CH1 and CL, if present in both the first and / or second polypeptide, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VH3-VL3-VH2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, and each of the first polypeptides has a structure represented by VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini. In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VH3-VL3-VH2-VL1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VL4, VH4-VL5-VH6-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VH6-VL6-VH5-VL4 -VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acids.In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VL3-VH3-VL2-VH1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VL4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4 The antibody has a structure represented by VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers. In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VH3-VL3-VH2-VL1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VH4-VH5-VL6-VH6-VL5-VL4 , VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VH3-VL3-VH2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4. , VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VH6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1 is linked to the carboxy terminus of the first and / or second polypeptide via one or more amino acid linkers. In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VH3-VL3-VH2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5 -VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6 -VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6- The polypeptide has a structure represented by VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and optionally, the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1, if present, is linked to the carboxy terminus of the first and / or second polypeptide via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VH3-VL3-VH2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VL6 H6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6- The polypeptide has a structure represented by VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1, if present, is linked to the carboxy terminus of the first and / or second polypeptide via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VH3-VL3-VH2-VL1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5 -VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and when CH1 and CL are present in both the first and / or second polypeptides, they are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VH3-VL3-VH2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5 -VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5- The polypeptide has a structure represented by VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each contain CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, CH1, CL, CH1-CL, or CL-CH1, if present, are linked to the carboxy termini of the first and / or second polypeptide via one or more amino acid linkers, and CH1 and CL, if present in both the first and / or second polypeptide, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VH3-VL3-VH2-VL1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VH4-VH5-VL6-VH6-VL5-VL4 , VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and CH1 and CL, if present in both the first and / or second polypeptides, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VH3-VL3-VH2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VL6 H6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6- The polypeptide has a structure represented by VH6-VH5-VL4, wherein the first and second polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1, if present, are linked to the carboxy termini of the first and / or second polypeptides via one or more amino acid linkers, and the CH1 and CL, if present in both the first and / or second polypeptides, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VH3-VL3-VH2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4; the first polypeptide and the second polypeptide each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini; VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers; VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers; CH1, CL, CH1-CL, or CL-CH1, if present, is linked to the carboxy termini of the first and / or second polypeptide via one or more amino acid linkers; and CH1 and CL, if present in both the first and / or second polypeptide, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VH3-VL3-VH2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, and each of the first polypeptides has a structure represented by VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini. In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VH3-VL3-VH2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH ... H4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each have a CH1, CL, CH at their carboxy termini. 1-CL, or CL-CH1, and VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acids. In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VH3-VL3-VH2-VH1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VL4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4 The antibody has a structure represented by VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VH3-VL3-VH2-VH1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VH4-VL5-VH6-VL6-VH5-VL4, VH4-VH5-VL6-VH6-VL5-VL4 , VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VH3-VL3-VH2-VH1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VL5-VH6-VL6-VH6-VL5-VL4, VH4-VL5-VH6-VL6-VH5-VL4, VH4-VL5-VH6-VL6-VH5-VL4, VH4-VL5-VH6-VL6-VH5-VL4, VH4-VH5-VL6-VH6-VL ... L4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1 is linked to the carboxy terminus of the first and / or second polypeptide via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VH3-VL3-VH2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5 -VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6 -VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6- The polypeptide has a structure represented by VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and optionally, the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1, if present, is linked to the carboxy terminus of the first and / or second polypeptide via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VH3-VL3-VH2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VL6 H6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6- The polypeptide has a structure represented by VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1, if present, is linked to the carboxy terminus of the first and / or second polypeptide via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VH3-VL3-VH2-VH1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5 -VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and when CH1 and CL are present in both the first and / or second polypeptides, they are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VH3-VL3-VH2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5 -VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5- The polypeptide has a structure represented by VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each contain CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, CH1, CL, CH1-CL, or CL-CH1, if present, are linked to the carboxy termini of the first and / or second polypeptide via one or more amino acid linkers, and CH1 and CL, if present in both the first and / or second polypeptide, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VH3-VL3-VH2-VH1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VH4-VL5-VH6-VL6-VH5-VL4, VH4-VH5-VL6-VH6-VL5-VL4 , VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and CH1 and CL, if present in both the first and / or second polypeptides, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VH3-VL3-VH2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VL6 H6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6- The polypeptide has a structure represented by VH6-VH5-VL4, wherein the first and second polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1, if present, are linked to the carboxy termini of the first and / or second polypeptides via one or more amino acid linkers, and the CH1 and CL, if present in both the first and / or second polypeptides, are linked to each other via one or more amino acid linkers. In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VH3-VL3-VH2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, V. L4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1 of the first polypeptide are , VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers; VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers; CH1, CL, CH1-CL, or CL-CH1, if present, are linked to the carboxy terminus of the first and / or second polypeptide via one or more amino acid linkers; and CH1 and CL, if both present in the first and / or second polypeptide, are linked to each other via one or more amino acid linkers. In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VL3-VH3-VL2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, and each of the first polypeptides has a structure represented by VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini.In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VL3-VH3-VL2-VL1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VL4, VH4-VL5-VH6-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VH6-VL6-VH5-VL4 -VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acids. In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VL3-VH3-VL2-VL1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4 The antibody has a structure represented by VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VL3-VH3-VL2-VL1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VH4-VH5-VL6-VH6-VL5-VL4 , VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VL3-VH3-VL2-VL1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VL4, VH4-VL5-VH6-VL6-VH5-VL4, VH4-VL5-VH6-VL6-VH5-VL4, VH4-VH5-VL6-VH6-VL ... L4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1 is linked to the carboxy terminus of the first and / or second polypeptide via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VL3-VH3-VL2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5 -VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6 -VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6- The polypeptide has a structure represented by VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and optionally, the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1, if present, is linked to the carboxy terminus of the first and / or second polypeptide via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VL3-VH3-VL2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VL6 H6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6- The polypeptide has a structure represented by VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1, if present, is linked to the carboxy terminus of the first and / or second polypeptide via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VL3-VH3-VL2-VL1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5 -VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and when CH1 and CL are present in both the first and / or second polypeptides, they are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VL3-VH3-VL2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5 -VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5- In some embodiments, the first polypeptide has a structure represented by VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, the CH1, CL, CH1-CL, or CL-CH1, when present, is linked to the carboxy termini of the first and / or second polypeptides via one or more amino acid linkers, and CH1 and CL, when both present in the first and / or second polypeptides, are linked to each other via one or more amino acid linkers. and the second polypeptide has a structure represented by VL1, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL6-VH5-VL4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VH6-VL6-VL5 -VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and CH1 and CL, if present in both the first and / or second polypeptides, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VL3-VH3-VL2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VL6 H6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6- The polypeptide has a structure represented by VH6-VH5-VL4, wherein the first and second polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1, if present, are linked to the carboxy termini of the first and / or second polypeptides via one or more amino acid linkers, and the CH1 and CL, if present in both the first and / or second polypeptides, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VL3-VH3-VL2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4; the first polypeptide and the second polypeptide each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini; VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers; VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers; CH1, CL, CH1-CL, or CL-CH1, if present, is linked to the carboxy termini of the first and / or second polypeptide via one or more amino acid linkers; and CH1 and CL, if present in both the first and / or second polypeptide, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VH3-VL3-VL2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, and each of the first polypeptides has a structure represented by VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini. In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VH3-VL3-VL2-VH1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VL4, VH4-VL5-VH6-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6 -VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acids.In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VH3-VL3-VL2-VH1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VL4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4 The antibody has a structure represented by VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers. In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VH3-VL3-VL2-VH1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VH4-VH5-VL6-VH6-VL5-VL4 , VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VH3-VL3-VL2-VH1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VL4, VH4-VL5-VH6-VL6-VH5-VL4, VH4-VL5-VH6-VL6-VH5-VL4, VH4-VH5-VL6-VH6-VL ... L4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1 is linked to the carboxy terminus of the first and / or second polypeptide via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VH3-VL3-VL2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5 -VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6 -VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6- The polypeptide has a structure represented by VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and optionally, the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1, if present, is linked to the carboxy terminus of the first and / or second polypeptide via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VH3-VL3-VL2-VH1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6 -VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to one or more amino acids. They are linked to each other via an amino acid linker, and CH1, CL, CH1-CL, or CL-CH1, when present, is linked to the carboxy terminus of the first and / or second polypeptide via one or more amino acid linkers. In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VH3-VL3-VL2-VH1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5 -VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and when CH1 and CL are present in both the first and / or second polypeptides, they are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VH3-VL3-VL2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5 -VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5- The polypeptide has a structure represented by VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each contain CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, CH1, CL, CH1-CL, or CL-CH1, if present, are linked to the carboxy termini of the first and / or second polypeptide via one or more amino acid linkers, and CH1 and CL, if present in both the first and / or second polypeptide, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VH3-VL3-VL2-VH1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VH4-VH5-VL6-VH6-VL5-VL4 , VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and CH1 and CL, if present in both the first and / or second polypeptides, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VH3-VL3-VL2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VL6 H6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6- The polypeptide has a structure represented by VH6-VH5-VL4, wherein the first and second polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1, if present, are linked to the carboxy termini of the first and / or second polypeptides via one or more amino acid linkers, and the CH1 and CL, if present in both the first and / or second polypeptides, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VH2-VH3-VL3-VL2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4; the first polypeptide and the second polypeptide each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini; VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers; VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers; CH1, CL, CH1-CL, or CL-CH1, if present, is linked to the carboxy termini of the first and / or second polypeptide via one or more amino acid linkers; and CH1 and CL, if present in both the first and / or second polypeptide, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VL3-VH3-VH2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, and each of the first polypeptides has a structure represented by VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini. In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VL3-VH3-VH2-VL1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VL4, VH4-VL5-VH6-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4 -VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acids.In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VL3-VH3-VH2-VL1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4 The antibody has a structure represented by VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers. In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VL3-VH3-VH2-VL1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VH4-VL5-VH6-VL6-VH5-VL4, VH4-VH5-VL6-VH6-VL5-VL4 , VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VL3-VH3-VH2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first peptide is and the second polypeptide each comprises a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide being linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1 being linked to the carboxy termini of the first and / or second polypeptide via one or more amino acid linkers. In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VL3-VH3-VH2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5. -VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6 -VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6- The polypeptide has a structure represented by VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and optionally, the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1, if present, is linked to the carboxy terminus of the first and / or second polypeptide via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VL3-VH3-VH2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VL6 H6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6- The polypeptide has a structure represented by VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1, if present, is linked to the carboxy terminus of the first and / or second polypeptide via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VL3-VH3-VH2-VL1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5 -VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and when CH1 and CL are present in both the first and / or second polypeptides, they are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VL3-VH3-VH2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5 -VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5- The polypeptide has a structure represented by VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each contain CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, CH1, CL, CH1-CL, or CL-CH1, if present, are linked to the carboxy termini of the first and / or second polypeptide via one or more amino acid linkers, and CH1 and CL, if present in both the first and / or second polypeptide, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VL3-VH3-VH2-VL1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VL4, VH4-VL5-VH6-VL6-VH5-VL4, VH4-VH5-VL6-VH6-VL5-VL4 , VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and CH1 and CL, if present in both the first and / or second polypeptides, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VL3-VH3-VH2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VL6 H6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6- The polypeptide has a structure represented by VH6-VH5-VL4, wherein the first and second polypeptides each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and the CH1, CL, CH1-CL, or CL-CH1, if present, are linked to the carboxy termini of the first and / or second polypeptides via one or more amino acid linkers, and the CH1 and CL, if present in both the first and / or second polypeptides, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VL3-VH3-VH2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4; the first polypeptide and the second polypeptide each comprise a CH1, CL, CH1-CL, or CL-CH1 at their carboxy termini; VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers; VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers; CH1, CL, CH1-CL, or CL-CH1, if present, is linked to the carboxy termini of the first and / or second polypeptide via one or more amino acid linkers; and CH1 and CL, if present in both the first and / or second polypeptide, are linked to each other via one or more amino acid linkers.

[0085] In some aspects, the antigen-binding polypeptide complex defined herein further comprises at least two of an Fc region, a CH1 region, and a CL region, optionally located at the carboxy terminus of the first polypeptide and / or the second polypeptide. For example, the carboxy terminus of the first polypeptide and / or the second polypeptide may comprise the structure CH1-Fc. For example, the carboxy terminus of the first polypeptide and / or the second polypeptide may comprise the structure CL-Fc. For example, the carboxy terminus of the first polypeptide and / or the second polypeptide may comprise the structure CL-CH1-Fc. For example, the carboxy terminus of the first polypeptide and / or the second polypeptide may comprise the structure CH1-CL-Fc. In some aspects, the first polypeptide may comprise at least two of an Fc region, a CH1 region, and a CL region at its C-terminus, and the second polypeptide may comprise an Fc region at its C-terminus. The Fc region, CH1 region, and / or CL region can be linked to the first polypeptide and / or the second polypeptide via at least one amino acid linker, and the Fc region, CH1 region, and / or CL region can be linked to each other via at least one amino acid linker. For example, the antigen-binding complex can comprise a first polypeptide and a second polypeptide, wherein the first polypeptide is VL1-VL2-VL3-VH3-VH2-VH1-CH1-Fc, VH1-VH2-VH3-VL3-VL2-VL1-CH1-Fc, VL1-VH2-VL3-VH3-VL2-VH1-CH1-Fc, VH1-VL2-VH3-VL3-VH2-VL1-CH1-Fc, VH1-VL2-VH3-VL3-VH2-VL1-CH1-Fc, VL1-VL2-VH3-VL3-VH2-VL1-CH1-Fc, VL1-VL2-VH3-VL3-VH2-VH1-CH1-Fc, VH1-VL2-VH3-VL3-VH2-VH1-CH1-Fc, VH1-VH2-VL3-VH3-VL2 -VL1-CH1-Fc, VL1-VH2-VH3-VL3-VL2-VH1-CH1-Fc, VH1-VL2-VL3-VH3-VH2-VL1-CH1-Fc, VL1-VL2-VL3-VH3-VH2-VH1-CL-Fc, VH1-VH2- VH3-VL3-VL2-VL1-CL-Fc, VL1-VH2-VL3-VH3-VL2-VH1-CL-Fc, VH1-VL2-VH3-VL3-VH2-VL1-CL-Fc, VL1-VL2-VH3-VL3-VH2-VH1-CL-Fc,VH1-VH2-VL3-VH3-VL2-VL1-CL-Fc、VL1-VH2-VH3-VL3-VL2-VH1-CL-Fc 、VH1-VL2-VL3-VH3-VH2-VL1-CL-Fc、VL1-VL2-VL3-VH3-VH2-VH1-CH1-C L-Fc、VH1-VH2-VH3-VL3-VL2-VL1-CH1-CL-Fc、VL1-VH2-VL3-VH3-VL2-V H1-CH1-CL-Fc、VH1-VL2-VH3-VL3-VH2-VL1-CH1-CL-Fc、VL1-VL2-VH3-V L3-VH2-VH1-CH1-CL-Fc、VH1-VH2-VL3-VH3-VL2-VL1-CH1-CL-Fc、VL1- VH2-VH3-VL3-VL2-VH1-CH1-CL-Fc、VH1-VL2-VL3-VH3-VH2-VL1-CH1-CL -Fc、VL1-VL2-VL3-VH3-VH2-VH1-CL-CH1-Fc、VH1-VH2-VH3-VL3-VL2-VL 1-CL-CH1-Fc、VL1-VH2-VL3-VH3-VL2-VH1-CL-CH1-Fc、VH1-VL2-VH3-VL 3-VH2-VL1-CL-CH1-Fc、VL1-VL2-VH3-VL3-VH2-VH1-CL-CH1-Fc、VH1-VH2-VL3-VH3-VL2-VL1-CL-CH1-Fc、VL1-VH2-VH3-VL3-VL2-VH1-CL-CH1-Fc、VH1-VL2-VL3-VH3-VH2-VL1-CL-CH1-Fc、VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CH1-Fc、VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL 1-CH1-Fc、VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CH1-Fc、VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CH1-Fc、VL1-L1-VL2-L2-VH3- L3-VL3-L4-VH2-L5-VH1-CH1-Fc、VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CH1-Fc、VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CH1-Fc、VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CH1-Fc、VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CL-Fc、VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L 5-VL1-CL-Fc、VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CL-Fc、VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CL-Fc、VL1-L1-VL2-L2-VH3-L3-V L3-L4-VH2-L5-VH1-CL-Fc、VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CL-Fc、VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CL-Fc、VH1-L1-VL2- L2-VL3-L3-VH3-L4-VH2-L5-VL1-CL-Fc、VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CH1-CL-Fc、VH1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VL1-CH1 -CL-Fc、VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CH1-CL-Fc、VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CH1-CL-Fc、VL1-L1-VL2-L2-VH3-L 3-VL3-L4-VH2-L5-VH1-CH1-CL-Fc、VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CH1-CL-Fc、VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CH1-CL -Fc、VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CH1-CL-Fc、VL1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VH1-CL-CH1-Fc、VH1-L1-VH2-L2-VH3-L3-V L3-L4-VL2-L5-VL1-CL-CH1-Fc、VL1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VH1-CL-CH1-Fc、VH1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VL1-CL-CH1-Fc、It has a structure represented by VL1-L1-VL2-L2-VH3-L3-VL3-L4-VH2-L5-VH1-CL-CH1-Fc, VH1-L1-VH2-L2-VL3-L3-VH3-L4-VL2-L5-VL1-CL-CH1-Fc, VL1-L1-VH2-L2-VH3-L3-VL3-L4-VL2-L5-VH1-CL-CH1-Fc, or VH1-L1-VL2-L2-VL3-L3-VH3-L4-VH2-L5-VL1-CL-CH1-Fc, and the second polypeptide is Fc, VL4-VH4-CH1-Fc, VL4-VH4-CL-Fc, VL4-VH4-CH1-CL-Fc, VL4-VH4-CL-CH1-Fc, VH4-VL4-CH1-Fc, VH4-VL4-CL-Fc, VH4-VL4-CH1-CL-Fc, VH4-VL4-CL-CH1-Fc, VL4-L6-VH4-CH1-Fc, VL4-L6-VH4-CL-Fc, VL4-L6-VH4-CH1-CL-Fc, VL4-L6-VH4-CL-CH1-Fc, VH4-L6-VL4-CH1-Fc, VH4-L6-VL4-CL-Fc, VH4-L6-VL4-CH1-CL-Fc, VH4-L6-VL4-CL-CH1-Fc, VL4-VL5-VH5-VH4-CH1-Fc, VL4-VL5-VH5-VH4-CL-Fc, VL4-VL5-VH5-VH4-CH1-CL-Fc, VL4-VL5-VH5-VH4-CL-CH1-Fc, VH4-VH5-VL5-VL4-CH1-Fc, VH4-VH5-VL5-VL4-CL-Fc, VH4-VH5-VL5-VL4-CH1-CL-Fc, VH4-VH5-VL5-VL4-CL-CH1-Fc, VL4-L6-VL5-L7-VH5-L8-VH4-CH1-Fc, VL4-L6-VL5-L7-VH5-L8-VH4-CL-Fc, VL4-L6-VL5-L7-VH5-L8-VH4-CH1-CL-Fc, VL4-L6-VL5-LVL4-VL5-VL6-VH6-VH5-VH4-CL-Fc、VL4-VL5-VL6-VH6-VH5-VH4-CH1-CL-Fc、VL4-VL5-VL6-VH6-VH5-VH4-CL-CH1-Fc、VH4-VH5-VH6-VL6-VL5-VL4-CH1-Fc、VH4-VH5-VH6-VL6-VL5-VL4-CL-Fc、VH4-VH5-VH6-VL6-VL5-VL4-CH1-CL-Fc、VH4-VH5-VH6-VL6-VL5-VL4-CL-CH1-Fc、VL4-VH5-VL6-VH6-VL5-VH4-CH1-Fc、VL4-VH5-VL6-VH6-VL5-VH4-CL-Fc、VL4-VH5-VL6-VH6-VL5-VH4-CH1-CL-Fc、VL4-VH5-VL6-VH6-VL5-VH4-CL-CH1-Fc、VH4-VL5-VH6-VL6-VH5-VL4-CH1-Fc、VH4-VL5-VH6-VL6-VH5-VL4-CL-Fc、VH4-VL5-VH6-VL6-VH5-VL4-CH1-CL-Fc、VH4-VL5-VH6-VL6-VH5-VL4-CL-CH1-Fc、VL4-VL5-VH6-VL6-VH5-VH4-CH1-Fc、VL4-VL5-VH6-VL6-VH5-VH4-CL-Fc、VL4-VL5-VH6-VL6-VH5-VH4-CH1-CL-Fc、VL4-VL5-VH6-VL6-VH5-VH4-CL-CH1-Fc、VH4-VH5-VL6-VH6-VL5-VL4-CH1-Fc、VH4-VH5-VL6-VH6-VL5-VL4-CL-Fc、VH4-VH5-VL6-VH6-VL5-VL4-CH1-CL-Fc、VH4-VH5-VL6-VH6-VL5-VL4-CL-CH1-Fc、VL4-VH5-VH6-VL6-VL5-VH4-CH1-Fc、VL4-VH5-VH6-VL6-VL5-VH4-CL-Fc、VL4-VH5-VH6-VL6-VL5-VH4-CH1-CL-Fc、VL4-VH5-VH6-VL6-VL5-VH4-CL-CH1-Fc、VH4-VL5-VL6-VH6-VH5-VL4-CH1-Fc、VH4-VL5-VL6-VH6-VH5-VL4-CL-Fc、VH4-VL5-VL6-VH6-VH5-VL4-CH1-CL-Fc、VH4-VL5-VL6-VH6-VH5-VL4-CL-CH1-Fc、VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-CH1-Fc, VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-CL-Fc, VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-CH1-CL-Fc, VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-, VH4-CL-CH1-Fc, VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-CH1-Fc, VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-CL-Fc, VH4-L6-VH5-L7-V H6-L8-VL6-L9-VL5-L10-VL4-CH1-CL-Fc, VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-CL-CH1-Fc, VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-CH1-Fc, VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-CL-Fc, VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-CH1-CL-Fc, VL4-L6-VH5-L7-VL 6-L8-VH6-L9-VL5-L10-VH4-CL-CH1-Fc、VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-CH1-Fc、VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-CL -Fc、VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-CH1-CL-Fc、VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-CL-CH1-Fc、VL4-L6-VL5-L7-VH6- L8-VL6-L9-VH5-L10-VH4-CH1-Fc, VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4-CL-Fc, VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4-CH1-CL-F c, VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4-CL-CH1-Fc, VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4-CH1-Fc, VH4-L6-VH5-L7-VL6-L8-VH 6-L9-VL5-L10-VL4-CL-Fc、VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4-CH1-CL-Fc、VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4-CL-CH1-Fc、VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4-CH1-Fc, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4-CL-Fc, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4-CH1-CL-Fc, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4-CL-CH1-Fc, VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-CH1-Fc VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-CL-Fc, VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-CH1-CL-Fc, VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-CL-CH1-Fc, VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-L11-CH1-Fc, VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-L1 1-CL-Fc、VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-L11-CH1-CL-Fc、VL4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VH4-L11-CL-CH1-Fc、VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-L11-CH1-Fc、VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-L11-CL-Fc、VH4-L6-VH5-L7-VH6-L8-VL 6-L9-VL5-L10-VL4-L11-CH1-CL-Fc、VH4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VL4-L11-CL-CH1-Fc、VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-L11-CH1-Fc、VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-L11-CL-Fc、VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-L11-CH1-CL-Fc、VL4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VH4-L11-CL-CH1-Fc、VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-L11-CH1-Fc、VH4-L6-VL5-L7-VH6-L 8-VL6-L9-VH5-L10-VL4-L11-CL-Fc、VH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VL4-L11-CH1-CL-Fc、またはVH4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10- VL4-L11-CL-CH1-Fc, VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4-L11-CH1-Fc, VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4-L11-CL-Fc, VL4-L 6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4-L11-CH1-CL-Fc、VL4-L6-VL5-L7-VH6-L8-VL6-L9-VH5-L10-VH4-L11-CL-CH1-Fc、VH4-L6-VH5-L7-VL6-L8-V H6-L9-VL5-L10-VL4-L11-CH1-Fc, VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4-L11-CL-Fc, VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4-L11-C H1-CL-Fc, VH4-L6-VH5-L7-VL6-L8-VH6-L9-VL5-L10-VL4-L11-CL-CH1-Fc, VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4-L11-CH1-Fc, VL4-L6-VH5 -L7-VH6-L8-VL6-L9-VL5-L10-VH4-L11-CL-Fc、VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL5-L10-VH4-L11-CH1-CL-Fc、VL4-L6-VH5-L7-VH6-L8-VL6-L9-VL 5-L10-VH4-L11-CL-CH1-Fc、VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-L11-CH1-Fc、VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-L11-CL-Fc、and VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-L11-CH1-CL-Fc, or VH4-L6-VL5-L7-VL6-L8-VH6-L9-VH5-L10-VL4-L11-CL-CH1-Fc, wherein VL1 is a first immunoglobulin light chain variable region, VL2 is a second immunoglobulin light chain variable region, VL3 is a third immunoglobulin light chain variable region, VL4 is a fourth immunoglobulin light chain variable region, VL5 is a fifth immunoglobulin light chain variable region, and VL6 is a sixth immunoglobulin light chain variable region; VH1 is a first immunoglobulin heavy chain variable region, VH2 is a second immunoglobulin heavy chain variable region, VH3 is a third immunoglobulin heavy chain variable region, VH4 is a fourth immunoglobulin heavy chain variable region, VH5 is a fifth immunoglobulin heavy chain variable region, and VH6 is a sixth immunoglobulin heavy chain variable region, Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge, CH1 is heavy chain constant region 1, CL is a light chain constant region, and L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, and L11 are amino acid linkers. In some aspects, the first polypeptide has a structure represented by VL1-VL2-VL3-VH3-VH2-VH1, and the second polypeptide has a structure represented by Fc, wherein the first polypeptide comprises CH1-Fc, CL-Fc, CH1-CL-Fc, or CL-CH1-Fc at its carboxy terminus, and optionally, the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers. In some aspects, a first polypeptide has a structure represented by VH1-VH2-VH3-VL3-VL2-VL1, and a second polypeptide has a structure represented by Fc, wherein the first polypeptide comprises CH1-Fc, CL-Fc, CH1-CL-Fc, or CL-CH1-Fc at its carboxy terminus, and optionally, VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide areIn some embodiments, the first polypeptide has a structure represented by VL1-VH2-VL3-VH3-VL2-VH1, and the second polypeptide has a structure represented by Fc, wherein the first polypeptide comprises CH1-Fc, CL-Fc, CH1-CL-Fc, or CL-CH1-Fc at its carboxy terminus, and optionally the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers. In some aspects, the first polypeptide has a structure represented by VH1-VL2-VH3-VL3-VH2-VL1, and the second polypeptide has a structure represented by Fc, wherein the first polypeptide comprises CH1-Fc, CL-Fc, CH1-CL-Fc, or CL-CH1-Fc at its carboxy terminus, and optionally, the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers. In some aspects, the first polypeptide has a structure represented by VL1-VL2-VH3-VL3-VH2-VH1, and the second polypeptide has a structure represented by Fc, wherein the first polypeptide comprises CH1-Fc, CL-Fc, CH1-CL-Fc, or CL-CH1-Fc at its carboxy terminus, and optionally, the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers. In some aspects, a first polypeptide has a structure represented by VH1-VH2-VL3-VH3-VL2-VL1, and a second polypeptide has a structure represented by Fc, wherein the first polypeptide comprises CH1-Fc, CL-Fc, CH1-CL-Fc, or CL-CH1-Fc at its carboxy terminus, and optionally the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers. In some aspects, a first polypeptide has a structure represented by VL1-VH2-VH3-VL3-VL2-VH1, and a second polypeptide has a structure represented by Fc, wherein the first polypeptide comprises CH1-Fc, CL-Fc, CH1-CL-Fc, or CL-CH1-Fc at its carboxy terminus, and optionally the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers.and optionally, the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers. In some embodiments, the first polypeptide has a structure represented by VH1-VL2-VL3-VH3-VH2-VL1, and the second polypeptide has a structure represented by Fc, and the first polypeptide has a structure represented by and optionally, the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers. In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VL3-VH3-VH2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5. -VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6 -VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6- and VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise CH1-Fc, CL-Fc, CH1-CL-Fc, or CL-CH1-Fc at their carboxy termini, and optionally, VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers, and / or VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VL3-VH3-VH2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL VH4-VL5-VH6-VL6-VH5-VL4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VH5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4 wherein the first polypeptide and the second polypeptide each comprise a CH1, CH1-Fc, CL-Fc, CH1-CL-Fc, or CL-CH1-Fc at their carboxy termini; VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers; and / or VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, when present, are linked to each other via one or more amino acid linkers; and CH1-Fc, CL-Fc, CH1-CL-Fc, or CL-CH1-Fc, when present in the second polypeptide, is linked to the carboxy terminus of the second polypeptide via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VL3-VH3-VH2-VH1 and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VL4, VH4-VL5-VH6-VL6-VH6-VL5-VL4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH6-VL6-VH4, VL ... The antibody has a structure represented by H5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first polypeptide and the second polypeptide each comprise CH1-Fc, CL-Fc, CH1-CL-Fc, or CL-CH1-Fc at their carboxy termini, and the VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acids.In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VL3-VH3-VH2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4 , VH4-VH5-VH6-VL6-VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-V L4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5- and VH4, or VH4-VL5-VL6-VH6-VH5-VL4, wherein the first and second polypeptides each comprise CH1-Fc, CL-Fc, CH1-CL-Fc, or CL-CH1-Fc at their carboxy termini, and the VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, if present, are linked to each other via one or more amino acid linkers, and optionally the CH1-Fc, CL-Fc, CH1-CL-Fc, or CL-CH1-Fc, if present, is linked to the carboxy terminus of the second polypeptide via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VL1-VL2-VL3-VH3-VH2-VH1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5-VH4, VH4-VH5-VH6-VL6- VL5-VL4, VL4-VH5-VL6-VH6-VL5-VH4, VH4-VL5-VH6-VL6-VH5-VL4, VL4-VL5-VH6-VL6-VH5-VH4, VH4-VH5-VL6-VH6-VL5-VL4, VL4-VH5-VH6-VL6-VL5-VH4, or VH4-VL5-VL6-VH6-VH5-VL4 wherein the first polypeptide and the second polypeptide each comprise a CH1, CH1-Fc, CL-Fc, CH1-CL-Fc, or CL-CH1-Fc at their carboxy termini; VL1, VL2, VL3, VH1, VH2, and VH3 of the first polypeptide are linked to each other via one or more amino acid linkers; VL4, VL5, VL6, VH4, VH5, and VH6 of the second polypeptide, when present, are linked to each other via one or more amino acid linkers; and optionally, CH1-Fc, CL-Fc, CH1-CL-Fc, or CL-CH1-Fc, when present, is linked to the carboxy terminus of the second polypeptide via one or more amino acid linkers.In some embodiments, the first polypeptide has a structure represented by VH1-VH2-VH3-VL3-VL2-VL1, and the second polypeptide has a structure represented by VL4-VH4, VH4-VL4, VL4-VL5-VH5-VH4, VH4-VH5-VL5-VL4, VL4-VL5-VL6-VH6-VH5 -VH4, VH4-VH5-VH6-VL6-VL...

Claims

1. 1. An antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide, the first polypeptide is and having a structure represented by the second polypeptide is and having a structure represented by where: VL1 is a first immunoglobulin light chain variable region; VL2 is a second immunoglobulin light chain variable region, VL3 is a third immunoglobulin light chain variable region, VL4 is a fourth immunoglobulin light chain variable region, VL5 is a fifth immunoglobulin light chain variable region, VL6 is a sixth immunoglobulin light chain variable region, VH1 is a first immunoglobulin heavy chain variable region; VH2 is a second immunoglobulin heavy chain variable region; VH3 is a third immunoglobulin heavy chain variable region; VH4 is a fourth immunoglobulin heavy chain variable region; VH5 is the fifth immunoglobulin heavy chain variable region; VH6 is the sixth immunoglobulin heavy chain variable region; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; CH1 is heavy chain constant region 1; CL is a light chain constant region, L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, and L12 are amino acid linkers; The antigen-binding polypeptide complex.

2. 1. An antigen-binding polypeptide complex comprising a first polypeptide and a second polypeptide, the first polypeptide is and having a structure represented by the second polypeptide is and having a structure represented by where: VL1 is a first immunoglobulin light chain variable region; VL2 is a second immunoglobulin light chain variable region, VL3 is a third immunoglobulin light chain variable region, VL4 is a fourth immunoglobulin light chain variable region, VL5 is a fifth immunoglobulin light chain variable region, VL6 is a sixth immunoglobulin light chain variable region, VH1 is a first immunoglobulin heavy chain variable region; VH2 is a second immunoglobulin heavy chain variable region; VH3 is a third immunoglobulin heavy chain variable region; VH4 is a fourth immunoglobulin heavy chain variable region; VH5 is the fifth immunoglobulin heavy chain variable region; VH6 is the sixth immunoglobulin heavy chain variable region; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; CH1 is heavy chain constant region 1; CL is a light chain constant region, L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, and L11 are amino acid linkers; The antigen-binding polypeptide complex.

3. An antigen-binding polypeptide having a structure represented by: where: VL1 is a first immunoglobulin light chain variable region; VL2 is a second immunoglobulin light chain variable region, VL3 is a third immunoglobulin light chain variable region, VH1 is a first immunoglobulin heavy chain variable region; VH2 is a second immunoglobulin heavy chain variable region; VH3 is a third immunoglobulin heavy chain variable region; CH3 is immunoglobulin heavy chain constant region 3; L1, L2, L3, L4, L5, L6, and L7 are amino acid linkers; The antigen-binding polypeptide complex.

4. 3. The antigen-binding polypeptide complex of claim 1 or 2, wherein VH1, VL1, VH4, and VL4 specifically bind to the same antigen, VH2, VL2, VH5, and VL5 specifically bind to the same antigen, and VH3, VL3, VH6, and VL6 specifically bind to the same antigen.

5. 3. The antigen-binding polypeptide complex of claim 1 or 2, wherein VL1, VL2, VL3, and VL4 specifically bind to different antigens.

6. The antigen-binding polypeptide complex of claim 5, wherein VL1, VL2, VL3, VL4, and VL5 specifically bind to different antigens.

7. 7. The antigen-binding polypeptide complex of claim 6, wherein VL1, VL2, VL3, VL4, VL5, and VL6 specifically bind to different antigens.

8. An antigen-binding polypeptide complex having a structure represented by the formula: where: VL1 is a first immunoglobulin light chain variable region; VL2 is a second immunoglobulin light chain variable region, VL3 is a third immunoglobulin light chain variable region, VH1 is a first immunoglobulin heavy chain variable region; VH2 is a second immunoglobulin heavy chain variable region; VH3 is a third immunoglobulin heavy chain variable region; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; L1, L2, L3, L4, L5, L6, and L7 are amino acid linkers; The antigen-binding polypeptide complex.

9. An antigen-binding polypeptide complex comprising a first polypeptide, a second polypeptide, and a third polypeptide, the first polypeptide is and having a structure represented by the second polypeptide is and having a structure represented by the third polypeptide is and having a structure represented by where: VL1 is a first immunoglobulin light chain variable region; VL2 is a second immunoglobulin light chain variable region, VL3 is a third immunoglobulin light chain variable region, VL4 is a fourth immunoglobulin light chain variable region, VL5 is a fifth immunoglobulin light chain variable region, VL6 is a sixth immunoglobulin light chain variable region, VH1 is a first immunoglobulin heavy chain variable region; VH2 is a second immunoglobulin heavy chain variable region; VH3 is a third immunoglobulin heavy chain variable region; VH4 is a fourth immunoglobulin heavy chain variable region; VH5 is the fifth immunoglobulin heavy chain variable region; VH6 is the sixth immunoglobulin heavy chain variable region; Fc is a region comprising immunoglobulin heavy chain constant region 2 (CH2), immunoglobulin heavy chain constant region 3 (CH3), and optionally an immunoglobulin hinge; CH1 is heavy chain constant region 1; CL is a light chain constant region, L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, and L13 are amino acid linkers; The antigen-binding polypeptide complex.

10. VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds an HIV protein; VL4 is a fourth immunoglobulin light chain variable region that specifically binds an HIV protein; VL5 is a fifth immunoglobulin light chain variable region that specifically binds an HIV protein; VL6 is a sixth immunoglobulin light chain variable region that specifically binds an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds an HIV protein; VH4 is a fourth immunoglobulin heavy chain variable region that specifically binds an HIV protein; VH5 is a fifth immunoglobulin heavy chain variable region that specifically binds an HIV protein; VH6 is a sixth immunoglobulin heavy chain variable region that specifically binds to an HIV protein; 10. The antigen-binding polypeptide complex of any one of claims 1, 2, and 9.

11. VL1 is a first immunoglobulin light chain variable region that specifically binds to an HIV protein; VL2 is a second immunoglobulin light chain variable region that specifically binds an HIV protein; VL3 is a third immunoglobulin light chain variable region that specifically binds an HIV protein; VH1 is a first immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH2 is a second immunoglobulin heavy chain variable region that specifically binds to an HIV protein; VH3 is a third immunoglobulin heavy chain variable region that specifically binds to an HIV protein; 9. An antigen-binding polypeptide complex according to claim 3 or 8.

12. The antigen-binding polypeptide complex of claim 10, wherein the HIV protein is an HIV envelope protein, an HIV structural protein, an HIV functional protein, or an HIV accessory protein.

13. The antigen-binding polypeptide complex of claim 12, wherein the HIV envelope protein is HIV envelope glycoprotein (Env), HIV envelope glycoprotein gp160, HIV envelope surface glycoprotein gp120, or HIV transmembrane envelope protein gp41.

14. The antigen-binding polypeptide complex of claim 12, wherein the HIV structural protein is p17, p24, p7, or p55.

15. The antigen-binding polypeptide complex of claim 12, wherein the HIV functional protein is p66, HIV-1 protease (PR), or p31.

16. The antigen-binding polypeptide complex of claim 12, wherein the HIV accessory protein is Nef, Tat, Rev, Vif, Vpr, or Vpu.

17. 10. The antigen-binding polypeptide complex of any one of claims 1, 2, 3, 8, and 9, which binds to an HIV protein with an equilibrium dissociation constant (KD) of about 10 μM to about 1 pM.

18. 10. The antigen-binding polypeptide complex of any one of claims 1, 2, 3, 8, and 9, which specifically binds to a viral peptide, protein, polypeptide, or fragment thereof.

19. 10. The antigen-binding polypeptide complex of any one of claims 1, 2, 3, 8, and 9, wherein the immunoglobulin hinge comprises an upper hinge region, a middle hinge region, a lower hinge region, or a combination thereof.

20. 10. The antigen-binding polypeptide complex of any one of claims 1, 2, 3, 8, and 9, wherein linker L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, and / or L13 has a length of from about 1 amino acid to about 50 amino acids.

21. The linkers L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, and / or L13 are (SEQ ID NOS: 1-19 and 679-686), or a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% identity to any one of SEQ ID NOS: 1-19 and 679-686.

22. 10. The antigen-binding polypeptide complex of any one of claims 1, 2, 3, 8, and 9, wherein the amino acid linker is non-immunogenic.

23. 10. The antigen-binding polypeptide complex of any one of claims 1, 2, 3, 8, and 9, wherein the amino acid linker does not contain a consensus T-cell epitope.

24. 10. The antigen-binding polypeptide complex of any one of claims 1, 2, 3, 8, and 9, wherein the Fc region comprises at least one knob-into-hole modification.

25. wherein the antigen-binding polypeptide complex is an IgG1 or IgG4 antibody, and the knob-into-hole modification is, based on the EU numbering scheme: (i) Knob substitutions of S354C and T366W, and hole substitutions of Y349C, T366S, L368A, and Y407V; (ii) hole substitutions at L234A, L235A, and P239A; (iii) hole substitutions at L234A and L235A; (iv) M428L and N433S hole substitutions; (v) M252Y, S254T, and T256E hole substitutions, or (vi) combinations thereof 25. The antigen-binding polypeptide complex of claim 24, comprising:

26. 10. The antigen-binding polypeptide complex of any one of claims 1, 2, 3, 8, and 9, comprising a detectable label.

27. 27. The antigen-binding polypeptide complex of claim 26, wherein the detectable label is a radioactive label, a chemiluminescent label, a fluorescent label, an enzyme, or a peptide tag, or a combination thereof.

28. 28. The antigen-binding polypeptide complex of claim 27, wherein the peptide tag is a polyhistidine tag consisting of about 4 to about 10 histidine residues.

29. 29. The antigen-binding polypeptide complex of claim 28, wherein the polyhistidine tag consists of approximately eight histidine residues.

30. 10. The antigen-binding polypeptide complex of any one of claims 1, 2, 3, 8, and 9, conjugated to a drug as an antibody-drug conjugate (ADC).

31. 31. The antigen-binding polypeptide complex of claim 30, wherein the agent is a cytotoxic agent, an immunomodulatory agent, an imaging agent, or a therapeutic protein, or a combination thereof.

32. Equilibrium dissociation constant (K Ｄ 10. The antigen-binding polypeptide complex of any one of claims 1, 2, 3, 8, and 9, which binds to an antigen at

33. An antibody or antigen-binding fragment thereof comprising an antigen-binding polypeptide complex according to any one of claims 1, 2, 3, 8, and 9.

34. 34. The antibody or antigen-binding fragment thereof of claim 33, wherein the antibody is IgG, IgM, IgE, IgA, or IgD.

35. The antibody or antigen-binding fragment thereof of claim 34, wherein the IgG is IgG1, IgG2, IgG3, or IgG4.

36. The antigen-binding fragment may be Fab, scFab, Fab', F(ab') ２ , Fv, or scFv.

37. 34. The antibody or antigen-binding fragment thereof of claim 33, wherein the antibody is a human antibody or a humanized antibody.

38. A chimeric antigen receptor (CAR) comprising the antigen-binding polypeptide complex of any one of claims 1, 2, 3, 8, and 9.

39. An immune cell comprising the CAR of claim 38.

40. A pharmaceutical composition comprising: (i) an antigen-binding polypeptide complex of any one of claims 1, 2, 3, 8, and 9; and (ii) a pharmaceutically acceptable carrier.

41. A kit comprising an antigen-binding polypeptide complex according to any one of claims 1, 2, 3, 8 and 9.

42. A pharmaceutical composition comprising an antigen-binding polypeptide complex of any one of claims 1, 2, 3, 8, and 9 for treating or preventing a disease or condition in a subject.

43. A pharmaceutical composition comprising an antigen-binding polypeptide complex of any one of claims 1, 2, 3, 8, and 9 for treating or preventing cancer in a subject.

44. A pharmaceutical composition comprising an antigen-binding polypeptide complex of any one of claims 1, 2, 3, 8, and 9 for treating or preventing a viral infection in a subject.

45. The pharmaceutical composition of claim 44, wherein the virus is human immunodeficiency virus (HIV).

46. 46. ​​The pharmaceutical composition of claim 45, wherein the HIV is HIV-1.

47. The virus may be an influenza virus, a respiratory syncytial virus (RSV), a chlamydia, an Adenoviridae, a Mastadenovirus, an Fowl Adenovirus, a Herpesviridae, a Herpes Simplex Virus 1, a Herpes Simplex Virus 2, a Herpes Simplex Virus 5, a Herpes Simplex Virus 6, a Leviviridae, a Levivirus, an Enterobacterium MS2, an Allorevirus, a Poxviridae, a Chordopoxvirinae, a Parapoxvirus, an Avian Poxvirus, a Capripoxvirus, a Leporipoxvirus, a Suipoxvirus, a Morsigma virus ... Poxvirus, Entomopoxvirinae, Papovaviridae, Polyomavirus, Papillomavirus, Paramyxoviridae, Paramyxovirus, Parainfluenza virus type 1, Morbillivirus, Measles virus, Rubulavirus, Mumps virus, Pneumovirinae, Pneumovirus, Metapneumovirus, Avian pneumovirus, Human metapneumovirus, Picornaviridae, Enterovirus, Rhinovirus, Hepatovirus, Human hepatitis A virus, Cardiovirus, Andapthovirus viruses, Reoviridae, Orthoreovirus, Orbivirus, Rotavirus, Cypovirus, Physivirus, Phytreovirus, Oryzavirus, Retroviridae, Mammalian Type B Retrovirus, Mammalian Type C Retrovirus, Avian Type C Retrovirus, Type D Retrovirus Group, BLV-HTLV Retrovirus, Lentivirus, HTLV-I and -II Virus, SARS Coronavirus, Herpes Simplex E Virus, Epstein-Barr Virus, Cytomegalovirus, Hepatitis Virus (HCV, HAV, HBV, HDV, HEV), Toxovirus Plasma gondiivirus, Treponema pallidum virus, Human T-lymphotropic virus, Encephalitis virus, West Nile virus, Dengue virus, Varicella-zoster virus, Measles, Mumps, Rubella, Spumavirus, Flaviviridae, Hepatitis C virus, Hepadnaviridae, Hepatitis B virus, Togaviridae, Alphavirus, Sindbis virus, Rubivirus, Rubella virus, Rhabdoviridae, Vesiculovirus, Lyssavirus, Ephemelovirus, Cytorhabdovirus, Nucleorhabdovirus, Arenaviridae, Arenavirus,45. The pharmaceutical composition of claim 44, wherein the virus is lymphocytic choriomeningitis virus, Yippi virus, Lassa virus, Coronaviridae, coronavirus, or torovirus.

48. A pharmaceutical composition comprising an antigen-binding polypeptide complex of any one of claims 1, 2, 3, 8, and 9 for treating or preventing acquired immune deficiency syndrome (AIDS).

49. A pharmaceutical composition comprising an antigen-binding polypeptide complex of any one of claims 1, 2, 3, 8, and 9 for treating or preventing AIDS-related complex (ARC).

50. A pharmaceutical composition comprising an antigen-binding polypeptide complex according to any one of claims 1, 2, 3, 8 and 9 for treating or preventing an HIV-associated opportunistic infection.