Binding multiple epitopes with a single antibody offers several benefits. For example, one specificity may target individual molecules whilst another could recruit effector cells or deliver a drug to the target. Other options include dual-target bispecifics which might detect a desired cell type with much higher selectivity than a monospecific antibody.
One of Absolute Antibody’s engineering services is the design and manufacture of multi-specific antibody formats. Starting with a hybridoma cell line or antibody sequence, we can deliver from milligrams to grams of antibody in as little as 8 weeks. Just contact us with any enquiries.
Knobs-into-Holes (KiH) – and other approaches
The most widely-recognised method for making bispecific antibodies is known as the Knobs-into-Holes (or KiH) approach. Two antibody chains are co-expressed recombinantly with mutations to create a “knob” on one and “hole” on the other such that heterodimer is the predominant product. When people refer to bispecific antibodies they are typically referring to these heterodimeric antibodies, i.e. a traditional IgG molecule but with one arm targeting one antigen and the other targeting a second.
However, by making use of Fab fragments and the single chain Fv (scFv) as building blocks, many other options become available. Some of these are summarised below.
You can learn more about multi-specific antibodies on our Antibody Resource.