>Bispecific antibody targets and more
Bispecific antibodies (bsAbs) harness the specificities of two antibodies and combine them to simultaneously recognize different antigens or epitopes. This 'two-target' functionality has meant that interest in their use for therapeutic applications has increased considerably. With the development and maturity of bsAb technology platform, the combination selection of targets is becoming the key point of competition. Among the bsAb programs under development currently, the combination of CD3 and tumor surface targets are the most popular targets pairs. And the new targets of Immune cell will also provide more choice in targets combination in the future.
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The characterization and pharmacokinetic (PK)/PD assessment are vital. Quality attributes such as antigen specificity; affinity and on- and off-rates; avidity (for bispecific antibodies that target two molecules on the same cell); potency; process-related impurities such as aggregates, fragments, and homodimers; stability; and half-life may affect pharmacology and should be studied. On the other hand, as bispecific antibodies may present as a mixture of biologically active and inactive forms, it is important to identify the bispecific antibody form(s) that is most pharmacologically relevant to PK/PD assessment and to develop validated assays that measure the appropriate form(s) accordingly. Due to the synergetic effect BsAb brings, the dosage is relatively low. Therefore, it requires a more sensitive assay for analysis.
Fig 1. Immobilized Human CD3E&CD3D Heterodimer Protein, His Tag&Tag Free (Cat. No. CDD-H52W1) at 2 μg/mL, add increasing concentrations of Bispecific T cell Engager (CD3 X BCMA) and then add Biotinylated BCMA Fc,Avitag (Cat. No. BC7-H82F0) at 0.2 μg/mL. Detection was performed using HRP-conjugated streptavidin with sensitivity of 4 ng/mL.
Fig 2. Binding assay between bsAb and Fc receptor
Fig 3. Immobilized Human OX40 Protein, His Tag (MALS verified) (Cat. No. OX0-H5224) at 2 μg/mL, add increasing concentrations of CTLA-4 x OX40 bispecific antibody in 50% Human serum and then add Biotinylated Human CTLA-4, Fc,Avitag (Cat. No. CT4-H82F3) at 0.2 μg/mL. Detection was performed using HRP-conjugated streptavidin with sensitivity of 4 ng/mL (Intact assay)
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