The Complete Guide to Classifications of Bispecific Antibodies

Ordinary tumor therapeutic antibodies can only bind to a single antigen with a relatively low binding specificity is relatively low, which is prone to off-target effects. Bispecific antibodies (bsAbs) can recognize and bind two different antigens separately, so it can connect immune cells, viral molecules, etc. to tumor cells, thereby enhancing the killing effect on target cells, and it can also combine different antigens on the same tumor cell to enhance its binding specificity, thereby reducing side effects such as off-target toxicity.

Antibodies are protein molecules containing heavy and light chains, which can be divided into a constant region (C region) and a variable region (V region), whereby bispecific antibodies can be classified according to whether they contain a constant region, and some bispecific antibodies contain a non-antibody fragment.

1 Bispecific antibody without C region

Such BsAbs contain only variable segments of antibody molecules, and thus their structures differ greatly from those of general antibodies, and can also be referred to as bispecific antibodies of non-IgG-like structures. It retains only the fragments that bind to the antigen and the relative molecular mass is usually small, so it has a high tissue permeability and easily penetrates into the tumor tissue through the blood vessels. However, low molecular mass also results in a short half-life in plasma, so the use of this drug for anti-tumor therapy requires continuous intravenous infusion of a constant-flow pump or in a sustained-release dosage form.

The variable region of heavy chain (VH) and the variable region of light chain (VL) are joined by a flexible peptide of 15-20 amino acids to form a single chain variable fragment (scFv). Two different scFv fragments can form a bispecific antibody without C region by a short peptide and connect T cells with tumor cells, thereby called Bispecific T cell Engager. Two single-chain antibody fragments consisting of VLA-VHA and VLB-VHB form two different conformations in space, respectively, and then bind to two different antigens, respectively. Studies have shown that tandem scFv fragments have the ability to recruit effector lymphocytes, such as anti-CD3 and anti-CD19 BiTEs, which turn out to be effective in the clinical treatment of several different B-cell lymphomas.

2 Bispecific antibody containing C region

The structure of this constant region-containing BsAbs is very similar to that of a general antibody structure, and is also called a bispecific antibody of an IgG-like structure. It differs from the general IgG antibody and non-IgG-like structure of bsAbs in that it has both bispecificity and the corresponding function of the constant region, and its relatively large molecular weight, so it has higher stability and longer half-life. And it is also beneficial for the purification of antibody products, but its tissue permeability is also relatively low. Different types can be formed depending on the different domains of the fusion, such as scFv-Fc antibody, Minibody, Bi-nanobody and the like.

The ScFv-Fc antibody (100-105 k) is a class of BsAbs containing both scFv and Fc segments. The scFv fragment can be fused to CH2 and CH3 of human IgG and can also be fused to the hinge region. Studies have shown that it has a certain effect in the treatment of tumors, and it also has certain small molecular characteristics, so it is convenient to use gene transfer technology to maintain its body content.

3 Bispecific antibodies containing non-antibody fragments

Some special non-antibody structures contained in some bispecific antibodies also play a certain role. For example, owing to the small molecular mass, some BsAbs have faster plasma clearance rate and shorter residence time in tumor tissues, which ultimately reduces their efficacy. Some researchers have linked some molecules in BsAbs by chemical ligation to increase their relative molecular mass, prolong their half-life, and thus improve their efficacy, such as linking polyethylene glycol (PEG), serum albumin and albumin binding groups. PEG is a polymer that increases the relative molecular mass of BsAbs and reduces its renal filtration rate. But in some cases, it may cause partial inactivation or decrease affinity of antibody fragments. In addition, it can also enhance the efficacy by connecting some drug molecules, such as diphtheria toxin, ricin, acacia toxin and so on.

Author Bio

As a supplier-of-choice for scientists across the globe, Creative Biolabs offers extensive service portfolio for bispecific antibody research. We are confident to provide customers first-class services that covers all kinds of research purposes. Creative Biolabs has been dedicated to the development of our techniques. Now, with the cutting-edge platforms and methods (quadroma development, chemical conjugation, and genetic engineering), a comprehensive list of bispecific antibody products is available to customers in academia and industry fields. According to modular architecture, Creative Biolabs is experienced in producing five major groups of bispecific molecules: bispecific IgGs, appended IgGs, BsAb fragments, bispecific fusion proteins and BsAb conjugates.

Creative Biolabs was founded by scientists who are dedicated to conquering cancer, optimizing the drug development process, leveraging accessible resources.