Generation of Anti-Idiotype scFv for Pharmacokinetic Measurement in Lymphoma Patients Treated with Chimera Anti-CD22 Antibody SM03

Abstract

Pre-clinical and clinical studies of therapeutic antibodies require highly specific reagents to examine their immune responses, bio-distributions, immunogenicity, and pharmacodynamics in patients. Selective antigen-mimicking anti-idiotype antibody facilitates the assessment of therapeutic antibody in the detection, quantitation and characterization of antibody immune responses. Using mouse specific degenerate primer pairs and splenocytic RNA, we generated an idiotype antibody-immunized phage-displayed scFv library in which an anti-idiotype antibody against the therapeutic chimera anti-CD22 antibody SM03 was isolated. The anti-idiotype scFv recognized the idiotype of anti-CD22 antibody and inhibited binding of SM03 to CD22 on Raji cell surface. The anti-idiotype scFv was subsequently classified as Ab2γ type. Moreover, our results also demonstrated firstly that the anti-idiotype scFv could be used for pharmacokinetic measurement of circulating residual antibody in lymphoma patients treated with chimera anti-CD22 monoclonal antibody SM03. Of important, the present approach could be easily adopted to generate anti-idiotype antibodies for therapeutic antibodies targeting membrane proteins, saving the cost and time for producing a soluble antigen.

Development and Characterization of a Neutralizing Anti-idiotype Antibody Against Mirvetuximab for Analysis of Clinical Samples

“…These findings are in good accordance with a report from Zhao and colleagues who have used β-class anti-idiotype antibodies in scFV format as surrogate antigen to overcome limitations related to expressing stable CD22 antigen. In cell-based competition assays, the authors report near complete inhibition of anti-CD22 antibody binding to CD22-positive Raji cells (19). Other reports suggest that the ability to compete with antigen binding can be rather diverse in an array of anti-idiotype antibodies and may be correlated with affinity (15).…”

“…Each approach has its advantages and can be successfully applied to raise useful tools for bioanalytical assays. For example, anti-idiotype scFv directed against the anti-CD22 antibody SM03 have been used to capture residual SM03 in serum levels of phase 1 patients (19). We used biolayer interferometry to characterize clone 4E12-G5, a technique that has been employed to rank the binding strength of anti-idiotype antibodies by off-rate screening, taking advantage of the fact that the binding off-rate is concentration independent and can be readily assessed in samples of differing antibody titers (14).…”

Quantitation and Identification of Therapeutic Anti-CD22 Monoclonal Antibodies in a Cell-Based ELISA Method

“…For example, ELISA assays based on whole live cells [ 4 , 5 , 6 ] or fixed cells [ 6 , 7 , 8 ] have been used to characterize antibodies against cell surface antigens. Meanwhile, other methods based on anti-idiotype (anti-Id) antibodies [ 6 , 9 ], peptide conjugates [ 10 ], or flow cytometry [ 11 ] provide effective tools for monitoring the antibody production or PK of the administered antibody in the patients [ 12 ]. However, the development of anti-Id antibodies remains challenging, laborious, and time-consuming [ 13 , 14 ].…”

Rapid identification of anti-idiotypic mAbs with high affinity and diverse epitopes by rabbit single B-cell sorting-culture and cloning technology

“…In that context, anti-idiotypic reagent antibodies (anti-IDs or Ab2) have become one of the preferable options for bioanalytical applications at pre-clinical and clinical stages. Common approaches used to generate these types of reagent antibodies against Ab1 include in vivo hybridoma technology, in vitro phage-displayed immunized or synthetic antibody libraries [6][7][8]. In our experience these technologies work reasonably well for generation of anti-IDs but require extended timelines and often yield lownumber panels of super-high affinity monoclonal antibodies (mAbs) that lack epitope-binding diversity.…”