ArticleTheoretical biology & medical modelling2015
Effects of different interchain linkers on biological activity of an anti-prostate cancer single-chain bispecific antibody.
Article in Theoretical biology & medical modelling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 8 citations in OpenAlex.
- Bispecific antibodies in metastatic castration-resistant prostate cancer: therapeutic strategies and frontier advances.World journal of urology · 2025Review
- Atomically accurate de novo design of antibodies with RFdiffusion.bioRxiv : the preprint server for biology · 2025Article
- Advances in nanobody multimerization and multispecificity: from in vivo assembly to in vitro production.Biochemical Society transactions · 2025Review
- Effect of non-repetitive linker on in vitro and in vivo properties of an anti-VEGF scFv.Scientific reports · 2022Article
- Toward Drug-Like Multispecific Antibodies by Design.International journal of molecular sciences · 2020Review
- Design and Production of Bispecific Antibodies.Antibodies (Basel, Switzerland) · 2019Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA single-chain bispecific antibody (scBsAb; an engineered antibody), has promising clinical applications. Nonetheless, the effect of different interchain linkers on its activity is poorly understood.
methodsGene synthesis was used to splice the anti-γ-seminoprotein single-chain antibody (anti-γ-Sm scFv) gene with the anti-CD3 single-chain antibody (anti-CD3 scFv) gene via different interchain peptide linkers. The Phyre2 software was used to predict spatial configuration of different scBsAbs. Eukaryotic expression vectors carrying scBsAbs were constructed by molecular cloning techniques and these plasmids were transfected into HeLa cells with liposomes. scBsAbs were purified by Ni(2+)-NTA agarose and analysed for antigen binding by an enzyme-linked immunosorbent assay (ELISA). Blood pharmacokinetics and inhibition of prostate tumour growth in nude mice were analysed in in vivo experiments.
resultsBioinformatics analysis and prediction showed that none of the three linkers, Fc, 205C', and HSA, had a significant effect on protein folding of anti-γ-Sm scFv or anti-CD3 scFv. Nevertheless, the spatial structures of the three linkers were noticeably different. Anti-γ-Sm × anti-CD3 scBsAb with an Fc, 205C', or HSA linker was successfully constructed, and these antibodies had similar protein expression levels. ELISA showed that all the three scBsAbs bound to Jurkat cells and the LNCaP membrane antigen, although binding of (205C')scBsAb was weaker than that of the two parental scFvs (P < 0.05). In contrast, binding strength of (HSA)scBsAb and (Fc)scBsAb was close to that of the parental scFvs (P > 0.05). Pharmacokinetic analysis showed that the half-clearance time of the elimination phase (T(1/2β)) for (HSA)scBsAb was the longest: up to 4.4 h. Compared with γ-Sm ScFv, the three scBsAbs all had a much stronger inhibitory effect on the growth of prostate cancer (P < 0.05), but there were no significant differences among the three scBsAbs (P > 0.05).
conclusionsHSA is the optimal linker for the anti-γ-Sm × anti-CD3 scBsAb and may improve antigen-binding affinity of antibodies and prolong physiological retention time. Interchain linkers affect the function of scBsAbs; these effects may have important implications for construction of antibodies.
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