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.
Highlights
For the development of therapeutic antibodies that target membrane antigens, it is important that exogenous naıve soluble antigens are made available for use in quality evaluation and pharmacokinetic assessments of the administered antibodies during preclinical and clinical studies [1]
It should be noted that only mouse k light chains were amplified employing the present PCR protocol and included in the single chain Fv (scFv) library, since l light chains represent a small proportion of the murine immunoglobulin V gene repertoire
We showed that an anti-idiotype scFv Hc5 could act as a surrogate ligand for membrane protein CD22
Summary
For the development of therapeutic antibodies that target membrane antigens, it is important that exogenous naıve soluble antigens are made available for use in quality evaluation and pharmacokinetic assessments of the administered antibodies during preclinical and clinical studies [1]. In the event when such a naıve soluble antigen is not available or accessible, the development of a specific anti-idiotype (anti-Id) antibody could prove handy as a surrogate antigen for the above purposes [2,3,4]. The anti-Id antibody can be used as diagnostic reagents for monitoring the pharmacokinetics (PK) of the administered antibody in the circulation of patients. No existing evidence supports the use of scFv antibody as surrogate antigen for PK characterization of circulating therapeutic antibody in patients
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