From antibody discovery to preclinical candidates
MPS Antibody Discovery partnerships leverage Integral Molecular’s full suite of technologies to deliver highly characterized monoclonal antibody candidates that are ready to enter preclinical development. We apply our 20+ years of experience with membrane proteins for functional assay development, engineering, and characterization studies that enable lead selection and optimization.
The MPS platform delivers lead preclinical antibodies with desired characteristics such as:
✔Membrane proteome-wide specificity
✔Humanized
✔State-specific activity
✔Ortholog cross-reactivity
MPS suite of services delivering lead candidates
MPS is the only MAb discovery platform specifically built for multipass membrane protein targets. Our technologies enable robust immune responses against conserved proteins and deep screening to discover rare functional antibodies.
Our comprehensive capabilities and technologies ensure antibodies with the desired function are identified.
.png?width=2946&height=1385&name=Functional%20Assays%20(cropped).png)
Functional antibody identification
Integral Molecular has the expertise to develop functional assays necessary to evaluate your target-specific antibody interactions.- GPCR signaling. GPCRs represent one of the most important classes of drug targets. Multiple assays, including Ca-flux and cAMP, are offered to determine MAb activity against these important targets.
- Ion channel activity. Membrane potential sensing dyes and solute transport assays are used to determine agonist or antagonist activities of antibodies against ion channels and transporters.
- T cell activation. Primary immune cell assays are used for functional screening of MAbs and bispecific antibodies, including antibody and T cell dependent cellular cytotoxicity (ADCC, TDCC) for immuno-oncology targets and flow cytometry for immune cell activation and cytokine secretion. These types of assays can be used to evaluate and rank candidates’ ability to kill cancer cells through T cell mediated cytolysis.
Lead selection and characterization
Leads are selected based on binding characteristics, epitope location, and binding reactivity.- Biophysical characterization. Assays including thermostability, SEC, and binding kinetics by BLI biosensor are commonly applied to understand MAb biophysical properties.
- Epitope binning. These assays help to define an antibody’s biological significance by determining the area of the target molecule bound by your antibody. Detailed epitope mapping is performed using our Shotgun Mutagenesis technology.
- Ligand blocking. Competition assays are used to confirm that inhibitory antibodies impede ligand access to the binding site.
- Species ortholog testing. Antibodies are evaluated by flow cytometry for binding to species orthologues to determine cross-reactivity and appropriate preclinical animal models.
- Specificity. The Membrane Proteome Array™ (MPA) is used for comprehensive specificity profiling. MAbs are screened against 6,000 membrane proteins to identify any potential off-target binding interactions across the human membrane proteome.
Lead optimization
Leads are optimized for developability and preclinical testing using proprietary protein engineering approaches.- Affinity maturation. Engineering approaches are applied to improve the affinity and avidity for increased binding strength.
- Fc reformatting. Isolated humanized IgG MAbs can undergo Fc reformatting to bring the molecule one step closer to therapeutic development. This includes reformatting for bispecific antibodies.
Case Studies
P2X7 | Ion Channel
.png?width=241&height=241&name=PDF%20images%20for%20website%20(11).png)
Learn how the research team at Integral Molecular isolated agonist and antagonist MAbs targeting the P2X7 ion channel for autoimmune disorders.