Bispecific antibodies (BsAbs) are artificial antibodies that can simultaneously bind to two different antigens or epitopes, thereby enhancing their therapeutic potential. Conventional BsAbs are often difficult to produce and have unfavorable pharmacokinetic properties, such as low stability, high aggregation, and short half-life. To overcome these limitations, bispecific antibody fragments have been developed as smaller and simpler alternatives to BsAbs. Bispecific antibody fragments are composed of two or more antibody domains that retain the antigen-binding function, but lack the Fc region and other non-essential parts of the antibody molecule.
SdAb-HAS is a type of single-domain antibody (sdAb) that is fused with human serum albumin (HAS) to extend its half-life and improve its solubility. By fusing sdAbs with HAS, the resulting sdAb-HAS can benefit from the high stability and circulation time of HAS, as well as the high affinity and specificity of sdAbs. SdAb-HAS can also reduce the renal clearance and immunogenicity of sdAbs, which are common drawbacks of small antibody fragments. SdAb-HAS can be constructed to form bispecific sdAb-HAS by fusing two sdAbs with different specificities to the same HAS molecule.
Bispecific T-cell Engagers are composed of two scFvs, one that binds to CD3 on T cells and another that binds to a tumor-associated antigen. Bispecific T-cell engagers can bridge T cells and tumor cells, regardless of their MHC expression, and trigger T cell activation and cytotoxicity. Bispecific T-cell engagers have several advantages as bispecific antibody fragments, such as high potency, low toxicity, and easy production. Several bispecific T-cell engagers have been developed for cancer immunotherapy, such as blinatumomab and amivantamab, which have shown promising clinical outcomes.
Diabodies are formed by the dimerization of two scFvs with different specificities, resulting in a Y-shaped molecule with two antigen-binding sites. Diabodies have several advantages as bispecific antibody fragments, such as high stability, low aggregation, and easy production. However, diabodies also have some disadvantages, such as low affinity, low solubility, and low specificity. For cancer immunotherapy, several diabodies have been developed to induce tumor cell death by recruiting T cells or blocking signaling pathways.
Dual affinity re-rargetings are formed by the covalent fusion of two scFvs with different specificities, resulting in a V-shaped molecule with two antigen-binding sites. They have several advantages as bispecific antibody fragments, such as high affinity, high specificity, high solubility, and low immunogenicity. However, they also have some challenges, such as low stability, low potency, and short half-life. Several of them have been developed for cancer immunotherapy, which can effectively target tumor cells and activate T cells.
TandAbs are formed by the fusion of two scFvs with the same specificity, resulting in a U-shaped molecule with two antigen-binding sites. TandAbs have several advantages as bispecific antibody fragments, such as high avidity, high stability, and high solubility. However, TandAbs also have some limitations, such as high immunogenicity, high complexity, and low specificity. Several TandAbs have been developed to induce tumor cell death by recruiting T cells or blocking signaling pathways.
scDiabodies are similar to diabodies, but they are formed by the covalent fusion of two scFvs with different specificities, resulting in a Y-shaped molecule with two antigen-binding sites. scDiabodies have several advantages as bispecific antibody fragments, such as high stability, low aggregation, and easy production. However, scDiabodies also have some disadvantages, such as low affinity, low solubility, and low specificity. Also, several scDiabodies have been developed for cancer immunotherapy.
scDiabody-CH3 is a type of scDiabody that is fused with the CH3 domain of IgG to increase its half-life and stability. CH3 is the constant domain of the heavy chain of IgG that can form a stable dimer. By fusing scDiabodies with CH3, the resulting scDiabody-CH3 can benefit from the high stability and circulation time of CH3, as well as the high affinity and specificity of scDiabodies. scDiabody-CH3 can also reduce the renal clearance and immunogenicity of scDiabodies, which are common drawbacks of small antibody fragments. scDiabody-CH3 can be constructed to form bispecific scDiabody-CH3 by fusing two scDiabodies with different specificities to the same CH3 molecule. Some examples of scDiabody-CH3 are anti-CD3/anti-CD19 scDiabody-CH3 and anti-CD3/anti-CEA scDiabody-CH3, which can effectively target tumor cells and activate T cells.
Diabody-CH3 is a fusion protein of two diabodies connected together by a CH3 region, each diabody consists of a single-chain variable fragment (scFv) and an scFv. The VH and VL domains of the diabody form an inter-chain pairing. Each CH3 region is attached to a diabody with different specificities, which results in a 2+2 antigen-binding valency and extends the half-life of this bispecific antibody (BsAb) in serum. This BsAb can redirect natural killer (NK) cells to tumor cells. It is designed for the research of head and neck cancer, colorectal cancer, glioblastoma multiforme, squamous cell carcinoma, glioblastoma, medulloblastoma, non-small cell lung cancer, renal cell carcinoma and solid tumors therapy.
A triple body is a novel multifunctional antibody platform that consists of three scFvs with different target specificities, which can simultaneously recognize three different antigens or receptors. Its structural design and expression mode are different from the conventional BsAbs and trispecific antibodies (TsAbs), providing higher flexibility and stability. Triple bodies can be used for cancer immunotherapy, by targeting tumor cells, T cell activation receptor and T cell survival protein at the same time, enhancing the killing and persistence of T cells against tumor cells.
Miniantibody is a recombinant antibody composed of two single-chain Fv fragments linked by a CH3 domain and possessing different specificities. Compared with ordinary antibodies, Miniantibody has the advantages of smaller molecular weight, higher stability, and easier expression in E. coli. Miniantibody can effectively block the binding of the spike protein of SARS-CoV-2 to the ACE2 protein on the surface of human cells, thereby preventing viral infection. Miniantibody is a promising antiviral tool that can also be used to study, diagnose and treat other diseases.
Minibody antibodies are small molecules composed of two single-chain Fv fragments and two CH3 domains, which can achieve the binding of different specificity Fv fragments through heterodimerization process. Minibody antibodies have high affinity and low immunogenicity, and can be used to target various tumor cell surface antigens, such as GD2. Minibody antibodies can also be further developed into trivalent bispecific Minibody antibodies (Tribi minibody), adding an Fv fragment for recruiting effector cells, thereby enhancing the affinity and cytotoxicity of the antibody. Minibody antibodies and Tribi minibody antibodies are promising anti-tumor immunotherapy tools, which can improve the pharmacokinetic properties and reduce the side effects of conventional antibody-drug conjugates (ADCs).
TriBi minibody antibody is a novel type of bispecific antibody that can bind to two different targets at the same time, enhancing tumor targeting and immune activation. It consists of three single-chain Fv (scFv) fragments, two of which recognize the tumor antigen HER2/neu and one of which binds to the CD16 receptor on NK cells. By activating both NK cells and tumor cells, TriBi minibody antibody induces antibody-dependent cellular cytotoxicity (ADCC). Compared to conventional antibodies, TriBi minibody antibody has higher affinity, lower dose, longer half-life and better stability.
scFv-CH3 KIH is a type of bispecific antibody that can bind to two different antigens at the same time. It consists of two chains, each with an scFv and a CH3 domain. scFv is a single-chain variable fragment that recognizes and binds to antigens, while CH3 is the third domain of the constant region of human IgG1, which regulates Fc functions. scFv-CH3 KIH antibody uses the Knob-into-hole (KiH) technology, which introduces complementary structures of protrusions and holes on the CH3 domains, to promote the formation of heterodimers between the two chains. scFv-CH3 KIH antibody has bivalent binding ability, enhanced affinity and specificity, and retained Fc functions.
Fab-scFv is a type of antibody fragment that combines the features of Fab and scFv. Fab is the antigen-binding part of an antibody, which consists of one heavy chain and one light chain. scFv is a fusion of the variable regions of the heavy and light chains, which forms a single-chain molecule. Fab-scFv antibody is made by linking a Fab fragment and an scFv fragment together, which can have two different specificities for different antigens. Fab-scFv antibody is smaller than a full antibody, but larger than a Fab or scFv alone. It can be used for various applications, such as diagnostics, therapeutics, and research.
scFv-CH-CL-scFv is a recombinant antibody composed of two scFvs linked by a flexible linker peptide. The scFv-CH-CL-scFv antibody has some advantages that traditional mAb and scFv do not have, such as smaller molecular weight, stronger tissue penetration, faster blood clearance, and immunogenicity Lower. scFv-CH-CL-scFv antibodies are mainly used in cancer immunotherapy by constructing chimeric antigen receptors (CARs) to redirect T cells so that they can recognize and kill tumor cells.
The F(ab’)2 is a pepsin-digested full IgG antibody that removes most of the Fc fragment but retains part of the hinge region. F(ab’)2 antibodies have two antigen-binding Fab regions connected by disulfide bonds and are therefore bivalent. The average molecular weight of F(ab’)2 antibodies is approximately 110 kDa. They have advantages in specific applications, such as avoiding recognition by Fc receptors or protein A or protein G on living cells.
F(ab’)2-scFv2 is a type of bispecific antibody that can bind to two different antigens or epitopes at the same time. It has a F(ab’)2 fragment and a scFv fragment, which are connected by a hinge region. The F(ab’)2 fragment consists of two Fab fragments that have the same specificity, while the scFv fragment has a different specificity. The scFv fragment is fused to the C terminus of one of the Fab fragments. F(ab’)2-scFv2 antibody can be used for various applications, such as targeting tumor cells, blocking or activating signaling pathways, and delivering drugs or toxins.
scFv-KIH is a type of bispecific antibody that can bind to two different antigens or epitopes at the same time. It consists of two chains, each with a scFv and a CH3 domain. The scFv is the part that recognizes and binds to the antigen, while the CH3 domain is the part that regulates the Fc functions. scFv-KIH uses the knob-into-hole (KiH) technology, which creates complementary structures on the CH3 domains, to form stable heterodimers between the two chains. scFv-KIH has bivalent binding ability, Fc functions, and biocompatibility.
Fab-scFv-Fc is a type of bispecific antibody that consists of a Fab fragment and a scFv fragment fused to the N-terminus of each Fc chain. The Fab and scFv fragments can bind to different antigens, allowing the antibody to target multiple pathways or cell types. The Fc part can mediate effector functions such as antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC). Fab-scFv-Fc antibodies can be produced in eukaryotic cells using the KIH technology, which forces the Fc chains to form a heterodimer. Fab-scFv-Fc antibodies have been developed for various therapeutic applications, such as cancer, inflammation, and infectious diseases.
Tetravalent HCAb is a type of antibody that has four binding sites for different antigens. It is derived from the heavy chain-only antibodies (HCAbs) found in camelids, such as llamas and camels. These antibodies have only a heavy chain and a variable domain that can recognize and bind to antigens. By linking two variable domains with different specificities to a human IgG constant region, a tetravalent HCAb can be generated. This antibody format has advantages in tissue penetration, antigen binding, and stability.
scDiabody-Fc is a type of bispecific antibody that can bind to two different targets at the same time. It is composed of two single-chain diabodies (scDiabodies) that are connected by a linker and fused to an Fc region. The Fc region helps to extend the half-life and stability of the molecule. scDiabody-Fc can be used for various therapeutic applications, such as hemophilia A, malaria, and cancer. scDiabody-Fc is a novel and versatile platform for bispecific antibody engineering and development.
Diabody-Fc consists of a central Fc region with a diabody fused to its N-terminus and two Fabs fused to its C-terminus. The diabody and Fab modules do not interfere with each other, and can be combined in a modular way. Diabody-Fc has several advantages over conventional IgGs, such as higher potency, broader neutralization, longer half-life, and easier production. Diabody-Fc has been developed for the treatment of cancer and COVID-19 by targeting P-cadherin/CD3 and RBD/CD3, respectively.
Tandem scFv-Fc is a type of bispecific antibody that can bind to two different antigens. It is composed of two scFvs linked together and attached to a human Fc region. The Fc region can extend the half-life and enhance the effector functions of the BsAb. Tandem scFv-Fc can be produced by genetic engineering or chemical conjugation. It has potential applications in immunology, oncology, hematology, and other fields.
An intrabody is a type of antibody that is expressed and works inside the cell, binding to a specific target protein in different subcellular locations. Intrabodies can be used to interfere with, modulate, or study the functions of various proteins involved in diseases such as cancer, HIV, autoimmune disorders, and neurodegenerative diseases. Intrabodies are usually made of scFvs that are fused with localization signals to direct them to the desired compartment. Intrabodies can be selected by different methods and delivered by gene therapy or transgenic animals. Intrabodies are promising tools for functional genomics and therapeutic applications.
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