Fully Human Fabs to CD22 (bCAT1)
Using newly constructed antigen binding fragment (Fab) phage display libraries, Pitt researchers have identified and characterized fully human Fabs to the CD22-D7 domain, targeting the membrane-proximal immunoglobulin domain D7. These binders show nanomolar-level binding affinity to the recombinant D7 protein and specific binding to CD22-expressing lymphoma cell lines. Their sequences and binding epitopes are distinct from a highly clinically-successful monoclonal antibody, m971, previously discovered by the same lab. These binders have significant potential to be incorporated into CAR-T cells for leukemia and lymphoma treatment; in addition, these antibodies can be further developed into other therapeutic modalities, such as IgG1s, immunotoxins, and antibody drug conjugates.
Description
The cluster of differentiation-22 (CD22) is a transmembrane glycoprotein and sialic acid receptor found on most B cells that functions as an inhibitory receptor for B cell receptor (BCR) signaling, indicating its role in B cell function, survival, and apoptosis. Due to its B cell lineage-specific expression, CD22 has emerged as an ideal target for treating B cell malignancies, including most lymphomas and leukemias, and success has been demonstrated using monoclonal antibody-based therapeutics to target it. Interestingly, the efficacy of CD22-targeted mAb-based CAR-T cell therapy is shown to be critically dependent on the epitope location, with anti-CD22 mAbs targeting the most membrane-proximal domain/epitope exhibiting much higher killing activity than those targeting distal epitopes.Applications
• Treating B cell related cancers, including most leukemias and lymphomasAdvantages
• Broadly applicable to most B cell related cancers• High therapeutic potential in pediatric B cell cancers, in which lack of expression of cell surface targeting molecules frequently limits treatment options
• Targets the membrane proximal epitopes for maximum efficacy