Recent research published in mAbs, co-authored by Andrew R. M. Bradbury, Dr. Atul K. Tandon (CEO and Founder of NeoBiotechnologies), and Brittany Jones (Scientific Director, NeoBiotechnologies), sheds light on a critical limitation in the field of monoclonal antibody production: hybridoma-derived monoclonal antibodies are frequently not truly monospecific.
Every rabbit monoclonal antibody from NeoBiotechnologies undergoes a rigorous, fully in-house production cycle designed to ensure exceptional performance:
Out of 185 hybridoma cell lines analyzed, 31.9% expressed one or more additional productive heavy or light chain variable regions beyond the intended monoclonal pair. Only 68.1% of hybridomas were found to be free of such additional chains.
The presence of extra productive chains resulted in a mixture of antibody species. This degraded overall antibody specificity, reduced binding signal, and lowered signal-to-noise ratio as shown by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry studies.
Many scientists assume monoclonal antibodies to be inherently monospecific. In reality, the genetic diversity within hybridoma lines can lead to unpredictable cross-reactivities and inconsistent results, especially across different batches or clones.
The authors emphasize that sequence-defined recombinant antibodies offer a solution. By producing antibodies recombinantly and verifying their sequences, researchers can guarantee monospecificity and reproducibility in research and diagnostics.
Dr. Tandon and Brittany Jones (NeoBiotechnologies) contributed critical data and expertise to this multi-center analysis, highlighting NeoBiotechnologies’ commitment to transparency and scientific rigor in antibody validation and production.
“Of the hybridomas we evaluated, 126 (68.1%) contained no additional productive chains, while the remaining 59 (31.9%) contained one or more additional productive heavy or light chains. The expression of additional chains degraded properties of the antibodies, including specificity, binding signal and/or signal-to-noise ratio…”
This study—featuring Dr. Tandon and Brittany Jones of NeoBiotechnologies—provides the first systematic quantification of genetic diversity and non-monospecificity in commercial hybridomas. The findings underscore the importance of transitioning to sequence-defined recombinant antibodies for improved specificity and reproducibility. For antibody users in life sciences, biotechnology, and diagnostics, these results stress the need to demand thoroughly validated reagents—and to partner with companies committed to scientific integrity.
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