Test the specificity of your antibody against a cell-array of 6,000 human membrane proteins
The long-held assumption that antibodies are exquisitely specific is being re-examined since approximately 25% of monoclonal antibodies (MAbs) show polyspecificity and bind unintended targets (cross-reactivity). Polyspecificity is a major issue during antibody preclinical development, with off-target binding leading to poor pharmacokinetics and efficacy1. In the clinic, mistargeted therapeutic antibodies can have unexpected, and sometimes severe or even life-threatening toxicity. Unidentified cross-reactivity is especially dangerous for cell-killing therapeutic modalities such as CAR-T cell therapies, bispecifics, or antibody-drug conjugates (ADC).
“MPA technology quickly provided us with the reassurance that Abound Bio’s potent, neutralizing antibodies to SARS-CoV-2 did not bind off-target human membrane proteins which could be associated with toxicity.”
-John W. Mellors, MD, CEO, Abound Bio
De-risk lead selection using the MPA
Because off-target antibody binding can create costly liabilities during later stages of development, specificity screening is recommended in early preclinical development before selection of a final lead molecule. The Membrane Proteome Array (MPA) is the leading technology for specificity profiling of antibodies and other antibody-based therapeutics. The MPA is a cell-based array that contains the largest set of human membrane proteins assembled. The array encompasses 95% of the human membrane proteome and will precisely identify any proteins mistargeted by antibodies, providing a complete cross-reactivity risk assessment. The MPA can screen panels of candidate molecules to aid in lead selection, with a turnaround time of 4-8 weeks (including setup). The MPA has been widely used to determine specificity and preclinical safety of antibodies, CAR-T cell therapies, and other biotherapeutics2.
Features of the Membrane Proteome Array
- 6,000 membrane proteins representing ~95% of the membrane proteome
- Sensitive detection by flow cytometry using unfixed cells to prevent false positives and negatives
- Target validation by secondary titration analysis
- High compatibility with all biotherapeutics including antibodies, scFv, VHH, bispecifics, peptides, and CAR-T cell therapies
- Cunningham, O. et al. (2021) Polyreactivity and polyspecificity in therapeutic antibody development: risk factors for failure in preclinical clinical development campaigns. mAbs. 13(1): E1999195.
- Norden, D. and Doranz, B. Testing for Off-target Binding. In: Cavagnaro, JA., and Cosenza, ME. Translational Medicine: Optimizing Preclinical Safety Evaluation of Biopharmaceuticals. CRC Pres; 2021. doi.org/10.1201/9781003124542.
Learn how the MPA enabled rapid progression of a neutralizing SARS-CoV-2 MAb
In response to the COVID-19 pandemic, Abound Bio developed potent neutralizing monoclonal antibodies (MAbs) against SARS-CoV-2. To progress development of a lead MAb, the company sought reassurance that their preclinical candidate did not possess off-target reactivity to human membrane proteins that could result in toxic effects. Off-target reactivity of therapeutic MAbs has been observed with other SARS-CoV-2 MAbs, so testing across the membrane proteome helps to validate therapeutic safety.