The natural structure of monoclonal antibodies provides a variety of possibilities for biological coupling. Chemical and specific natural (non engineering) antibody coupling has some advantages. It can avoid the complexity of antibody specific site mutation and the possible challenges in the amplification and optimization of cell culture. Coupling sites according to the antibody sequence, the […]
Apoptosis inducer (BCL XL inhibitor) Overexpression of anti apoptotic Bcl-2 family members (including BCL XL) is one of the mechanisms for cancer cells to obtain apoptosis resistance. Drugs that block the BH3 binding domain on BCL XL can trigger cancer cell apoptosis. Telanstadine and its analogues Targeted spliceosome is a large ribonucleoprotein complex involved in […]
There are so many payloads, like MMAE, Calicheamicin, MMAF, DM1, SN-38 and Dxd. Pyrrole benzodiazepines and indole chlorobenzodiazepines Pyrrolo [2,1-c] [1,4] benzodiazepine (PBD) is a natural product with antitumor activity. Their mode of action is selective alkylation in small grooves of DNA, in which the N2 of guanine forms a covalent bond with the electrophilic […]
There are so many payloads, like MMAE, Calicheamicin, MMAF, DM1, SN-38 and Dxd. Calendula Auristatins is an important payload used in ADC. The most famous family member MMAE exists in two listed drugs, adcetris and Polivy. At present, more than 10 kinds of ADCs with calendula (such as MMAE) or methylcalendula f (MMAF) […]
Table2. Chemical triggers Conjugate linker is not only the molecular part forming covalent connection between antibody and small molecule payload, but also the key element with design properties in targeted drug therapy. The addition of linkers should not induce aggregation, and it is necessary to ensure acceptable PK characteristics, limit the premature release (stability) of […]
1. Mylotarg® (gemtuzumab ozogamicin) from Wyeth/Pfizer was the first ADC to reach the market. It is composed of a recombinant humanized anti-CD33 mAb (IgG4κ antibody hP67.6) covalently attached to a calicheamicin derived payload (N-acetyl-γ-calicheamicin 1,2-dimethyl hydrazine dichloride) via a pH-sensitive hydrazone linker. 2. Adcetris® (brentuximab vedotin) from Seagen (formerly Seattle Genetics), containing a CD30-specific mAb conjugated to […]
Tribodies are multifunctional recombinant antibody derivatives. The Fab fragment serves as a specific heterodimerization signal, and the two scFv fragments are each fused to a different Fab chain. In this way we obtain a molecule of intermediate molecular weight (100 kDa) which allows incorporating three different antibody fragments (Fig. 1). This manifold, tribody, can be […]
Diabody is a noncovalent dimer of single-chain Fv (scFv) fragment that consists of the heavy chain variable (VH) and light chain variable (VL) regions connected by a small peptide linker. Another form of diabody is single-chain (Fv)2 in which two scFv fragments are covalently linked to each other. bispecific bivalent dimers are produced by using two […]
Dual-affinity re-targeting proteins (DARTs) encompasses of two Fv fragments, containing two single antigen-binding sites formed when two Fv fragments heterodimerize. The Fv1 contains of a VH from antibody A and a VL from antibody B, whereas Fv2 contains VH from antibody B and VL from antibody A in the order of VL (1)-VH (2) and […]
A tandem scFv links two or more scFvs with the helical peptide linkers in the orientation NH2–VL1–VH1–(linker–VL2–VH2)n–COOH, resulting in a single chain bivalent and bi-specific molecule encoded by a single gene (Figure 2). Tandem scFv can be used to target two different antigens on two different cells, two different antigens on the same cell, or […]
