Test the specificity of your antibody against a cell-array of 6,000 human membrane proteins

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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).

Learn more about how an antibody can show surprising polyspecificity for unrelated proteins.   

“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

References  

  1. 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. 
  2. 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. 

Case Study 

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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.

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