What are the limitations of monoclonal and polyclonal antibodies?

Numerous studies have highlighted inconsistencies in experimental results when using both, monoclonal as well as polyclonal antibodies (Abs). These reproducibility issues in the data are caused due to various factors, primarily non-specific antibody binding and batch-to-batch variation

This variability is not uncommon in polyclonal antibodies as they are derived from animal serum and a different animal or immunization source is used to prepare each batch. What was unexpected however is that monoclonal antibodies, which are considered to be highly specific, can also exhibit variability. Hybridomas, for instance, have been found to express additional functional variable regions.

A comparison of 185 hybridomas revealed that 32% produced extra light and heavy chains, which led to non-specific binding by the antibodies that were generated, resulting in diminished binding signal and a reduced signal-to-noise ratio.

To address these challenges, a new generation of antibodies, known as recombinant antibodies, has been developed.