Tetravalent Heavy Chain-only Antibody (HCAb) Generation Service

Creative Biolabs possesses unchallenged experience in synthesis of tetravalent heavy chain-only antibodies (hcAbs). Multiple platforms of Creative Biolabs are elaborately integrated for providing customer an expected tetravalent hcAb with high affinity and low immunogenicity for both academic and clinical purposes.

Heavy Chain Only Antibody (HCAb)

Camelidae species, such as llamas, camels and alpacas, generate both classical immunoglobulin G (IgG) antibodies comprising a heavy chain and light chain (IgG1), and unconventional IgGs (IgG2 and IgG3) that comprise only a heavy chain (HCAbs). HCAbs bind antigens just via the variable domain of the heavy chain, hence enabling easy cloning of the DNA encoding this binding domain, which is named as a single-domain antibody or heavy-chain-only VH (VHH). The discovery of heavy chain antibodies has led to unprecedented opportunities in cancer therapy. Recombinant VHHs are small (about 15-20 kDa) and strictly monomeric, they are able to bind their target with nM affinity, as well as with being stable in an extensive pH and temperature ranges.

Figure 1. Diagram of a tetravalent hcAb structure.

Tetravalent HCAb

Unlike conventional mammal antibody, camelid HCAb only has a pair of heavy chains consisting of constant domain and variable domain. Benefited by its simple structure and tiny size, HCAb and its artificial derivatives are well-known for their outstanding performance in tissue penetrating, antigen recognizing and binding, and resistance to physical and chemical impact. To further enhance its effect, tetravalent HCAb is developed as a novel bispecific HCAb format. Usually, two VHH domains with distinct specificity are sub-cloned into a eukaryotic expression vector. Meanwhile, a DNA fragment coding a human IgG2 or IgG3 constant region without CH1 is introduced between VHH domains. As a result, artificial bispecific chains consisting of tandem VHH1, hCH2, hCH3 and VHH2 are expressed. Taking advantage of the interaction between human IgG constant regions, bispecific tetravalent antibodies can be effectively generated. These bispecific antibodies can keep the specificity and binding affinity of their parental antibodies. More importantly, the tetravalent complex is more effective at a lower dose, which would show more options for physicians in disease treatment.

With our outstanding recombinant antibody synthesis platform, we are confident of providing desired tetravalent hcAbs with experimentally verified high-affinity and reliable safety. Creative Biolabs also provides other various services regarding BsAbs development. Please feel free to contact us for more information and a detailed quote.

References

1. Laventie, B. J.; et al. Heavy chain-only antibodies and tetravalent bispecific antibody neutralizing Staphylococcus aureus leukotoxins. Proceedings of the National Academy of Sciences. 2011, 108(39): 16404-16409.
2. Moghimi, S. M.; et al. Heavy chain only antibodies: a new paradigm in personalized HER2+ breast cancer therapy. BioImpacts: BI. 2013, 3(1): 1-4.