title: 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.
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors.forename: Pui-Fan
authors.initials: PF
authors.lastname: Wong
authors.affiliation: School of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors.forename: Susanna S T
authors.initials: SS
authors.lastname: Lee
authors.affiliation: Institute of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Shui-On
authors.initials: SO
authors.lastname: Leung
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors.forename: Wing-Tai
authors.initials: WT
authors.lastname: Cheung
authors.affiliation: National Institutes for Food and Drug Control, Beijing, China.
authors.forename: Jun-Zhi
authors.initials: JZ
authors.lastname: Wang
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D000918:Antibody Specificity; D045744:Cell Line, Tumor; D005260:Female; D008223:Lymphoma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000097:blood / Q000276:immunology* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology*; D057127:Single-Chain Antibodies / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D000888:Antibodies, Anti-Idiotypic; D011993:Recombinant Fusion Proteins; D051918:Sialic Acid Binding Ig-like Lectin 2; D057127:Single-Chain Antibodies