4 types of bsAb bioassay platform based on MOA
Over 40 bsAb bioassay projects
Bispecific antibodies (bsAbs) are constituted two binding sites and recognize different antigens, or different epitopes on the same antigen. Comparing with monoclonal antibodies (mAbs), bsAbs can directly recruit effector cells to the site of disease, and possess higher binding avidity and less resistance to targets due to interaction with more than one epitopes.
GenScript ProBio offers well developed in vitro pharmacology solutions based on different MOAs (cell-engager, dual-target blockade, dual immunomodulators, cell surface protein bridging, etc.) for bsAbs screening and characterizing.
Cell surface protein bridging
Cell-engager bsAb can active and re-direct effector cell (cytotoxicity T cell, NK cell, etc.) to tumor associated antigen (TAA) cells, and result in the eradication of the malignant cell.
Based on MoA of cell-engager, GenScript ProBio offers target-overexpressing cell lines and diverse immune cells to evaluate the biological activity of bsAb in vitro.
* Tumor-associated antigens (TAA), which have elevated levels on tumor cells, but are also expressed at lower levels on healthy cells. Tumor-specific antigens (TSA), found on cancer cells only, not on healthy cells.
1. TDCC assay
Anti-CD3×TAA bsAb induced TAA-expressing cell lysis in a dose-dependent manner.
2. Reporter cell line assay
Anti-CD3×TAA bsAb activated T cell in a dose-dependent manner.
Anti-4-1BB×TAA bsAb reporter cell line assay
Anti-4-1BB×TAA bsAb significantly activated 4-1BB signaling in reporter cells upon co-culture with TAA-overexpressing CHO-K1 cells in a dose-dependent manner (left). However, anti-4-1BB×TAA bsAb showed weak activation of 4-1BB signaling when co-incubated with CHO-K1 cells (right).
As a potent immunotherapy for autoimmune diseases and cancer, blockading multiple pathological factors and pathways by bsAb is a promising approach in improved therapeutic efficacy.
VEGF & ANG2 cell signaling pathway assay
Compared with anti-ANG2 mAb or anti-VEGF mAb treatment alone, combination of anti-ANG2 mAb and anti-VEGF mAb showed synergetic reduction in p-AKT level induced by ANG2 and VEGF. This bioassay is suited to evaluate characterization of anti-ANG2×VEGF bsAb.
TNFα & IL17A chemokines release assay
Compared with anti-TNFα mAb or anti-IL17A mAb treatment alone, combination of anti-TNFα mAb and anti-IL17A mAb could more effectively inhibite TNF-α and IL-17a mediated CXCL1 production. This bioassay is suited to evaluate characterization of anti-TNFα×IL17A bsAb.
Because combination of immune checkpoint inhibitors have shown significant success in promoting immune responses against cancer and can result in tumor regression in many patients, bsAb targeting two immune checkpoints to activate immune cell has quickly become a research hotspot.
Based on MOA of dual immunomodulators, GenScript ProBio develops dual target reporter gene systems and primary immune cell assays to verify the synergistically bioactivities of bsAb compared to the treatment alone or combination of monovalent monoclonal antibody.
PD-1+CTLA4 combination bioassay
Compared with anti-PD-1 mAb or anti-CTLA4 mAb treatment alone, combination of anti-PD-1 mAb and anti-CTLA4 mAb could more effectively activated PD-1&CTLA4 reporter cell line. This bioassay is suited to evaluate characterization of anti-PD-1×CTLA4 bsAb.
PD-1+4-1BB combination bioassay
Compared with anti-PD-L1 mAb or anti-4-1BB mAb treatment alone, combination of anti-PD-L1 mAb and anti-4-1BB mAb could more effectively activated 4-1BB&PD-1/PD-L1 reporter cell line. This bioassay is suited to evaluate characterization of anti-4-1BB×PD-1/PD-L1 bsAb.
Through clustering targeting molecules to form antigen complexes and aggregations, protein bridging bsAbs can mimicking effects of natural agonist to activates signaling cascade (i.e., HEMLIBRA® restore the blood clotting cascade).
Based on MoA of cell surface protein bridging, GenScript ProBio offers customized approaches to evaluate your biological candidates.
Compared with anti-DR5 mAb treatment, anti-TAA×DR5 bsAb could kill tumor cells at low concentration (tumor cell growth inhibition rate at 0.002nM close to 80% ).
ProBio provides one-stop bsAb discovery from target validation to preclinical candidates(PCC) , including bsAb format design for different MOA and target , bsAb construction and expression, functional validation, in vivo assay and developability.