Generation of anti-idiotype scFv for pharmacokinetic measurement in lymphoma patients treated with chimera anti-CD22 antibody SM03

• Published in: PloS one Vol. 9; no. 5; p. e96697
• Main Authors: Zhao, Qi, Wong, Pui-Fan, Lee, Susanna S T, Leung, Shui-On, Cheung, Wing-Tai, Wang, Jun-Zhi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.05.2014; Public Library of Science (PLoS)
• Subjects: Animals; Antibodies, Anti-Idiotypic - genetics; Antibodies, Anti-Idiotypic - immunology; Antibodies, Anti-Idiotypic - isolation & purification; Antibody Specificity; Antigens; B cells; Binding sites; Biology and Life Sciences; Cancer; CD22 antigen; Cell Line, Tumor; Cell surface; Female; Health aspects; Immune response; Immunization; Immunogenicity; Immunoglobulins; Laboratory animals; Ligands; Lymphoma; Lymphoma - immunology; Lymphoma - metabolism; Lymphoma - pathology; Lymphoma - therapy; Measurement; Medicine and Health Sciences; Membrane proteins; Mice; Mimicry; Monoclonal antibodies; Patients; Phages; Pharmacodynamics; Pharmacokinetics; Pharmacology; Proteins; Quantitation; Reagents; Recombinant Fusion Proteins - blood; Recombinant Fusion Proteins - immunology; Recombinant Fusion Proteins - pharmacokinetics; Recombinant Fusion Proteins - therapeutic use; Ribonucleic acid; RNA; Sialic Acid Binding Ig-like Lectin 2 - immunology; Single-Chain Antibodies - genetics; Single-Chain Antibodies - immunology; Single-Chain Antibodies - isolation & purification; Tumors; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0096697

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.