cH IgG1 / κλ body involves the formation of in vitro display libraries with common heavy chains against two different antigens. κλ body share the same heavy chain but carry either κ or λ light chains. Three different chains (one heavy and two light) are then co-expressed in a single cell to generate a mixture containing two mAb species (one κ and one λ) and a BiAb containing a κ and λ light chain (Fig. 1.). A BiAb assembled in this manner can then be efficiently purified from the mAb species and other contaminants using highly selective affinity resins binding to either human κ or λ constant domains. A κλ-body includes a common heavy chain and two light chains (one kappa and one lambda) with distinct specificities. Meanwhile, it is noteworthy that all of these fragments are integrated without any artificial mutations or linkers. Therefore, κλ-bodies with full human IgG backbone and intact Fc have got attractive characteristics including potent functions, extended half-life, long term storage, increased stability and ease of large-scale manufacturing. Thus, κλ-bodies are considered to be a leading one among our diverse products. Antibodies in this format are ideally suited for therapeutic application in both benign and malignant diseases.
Formats of bispecific antibodies (BsAbs)
Many formats have been developed for BsAb generation as listed in the following table.
Format | Schematic structure | Description | Example BsAb | Trademark | Company |
---|---|---|---|---|---|
tandem VHH | Tandem VHH fragment-based BsAb | N/A | |||
tandem scFv | Tandem ScFv fragment-based BsAb | AMG330 | BiTETM | Amgen | |
Dual-affinity re-targeting antibody | Tandem domain-exchanged Fv (can also be used to fuse with Fc domain to create whole Abs) | Flotetuzumab | DARTTM | Macrogenics | |
Diabody | dimer of single-chain Fv (scFv) fragment | vixtimotamab | ReSTORETM | Amphivena Therapeutics | |
(scFv)2-Fab | a Fab domain and two scFv domains bind | A-337 | ITabTM | Generon/EVIVE Biotech | |
Rat–mouse hybrid IgG | Full-size IgG-like half antibodies from two different species | Catumaxomab | TriomabTM | Trion Pharma | |
Hetero heavy chain, Common light chain | Hetero heavy chain, Common light chain | Emicizumab | ART-IgTM | Genentech/ Chugai/Roche | |
Controlled Fab arm exchange | Recombin the parental half antibodies | JNJ-64007957 | DuobodyTM | Genmab/ Janssen | |
Hetero H, forced HL IgG1 | KIH technology for heterodimerization of 2 distinct H chains, replacing the native disulfide bond in one of the CH1-CL interfaces with an engineered disulfide bond to enhance the cognate of H and L paring | MEDI5752 | DuetMabTM | MedImmune/ AstraZeneca | |
cH IgG1 | Identical heavy chains; 2 different light chains: one kappa (κ) and one lambda (λ) | NI-1701 | κλ bodyTM | Novimmune SA | |
Hetero H, CrossMab | KIH technology; domain crossover of immunoglobulin domains in the Fab region | Vanucizumab | CrossMabTM | Roche | |
scFv-Fab IgG | Fab-Fc; ScFv-Fc | Vibecotamab; M802 | XmabTM (the engineered Fc to enhance the generation of heterodimeric Fc); YBODYTM | Xencor/Amgen; YZYBio | |
VH1-VH2-CH1-Fc1(G1) x VL2-VL1-CL-Fc2(G1) | 2 binding motif in one half antibody | SAR440234 | CODV-IgTM | Sanofi | |
VL1-CL1-VH2-CH2-Fc x VH1-CH1 x VL2-CL2 | 2 binding motif in one half antibody | EMB-01 | FIT-IgTM | EPIMAB BIOTHERAPEUTICS | |
VH-1-TCR Cα x VL-1-TCR Cβ; VH-2-CH-2-Fc x VL-2-CL-2 | KIH technology; TCR Cα/Cβ is used to substitute the CH1 and CL domain in one arm | WuXibodyTM | WuXi Biologics | ||
C-terminal linker of Fc | Link the other molecules at the C-terminal of Fc | APVO442 | ADAPTIR-FLEXTM | Aptevo Therapeutics | |
Fc antigen binding site | 2 natural binding sites; 2 additional binding sites in the Fc loop | FS118 | mAb2 | F-star Therapeutics |