Sun Lin, Palt Roman, Schütz Georg, Föderl-Höbenreich Esther, Brod Laura, Hermle Antonia, Lux Anja, Steinkellner Herta, Kallolimath Somanath
Department of Biotechnology and Food Sciences, Institute of Plant Biotechnology and Cell Biology, BOKU University, Muthgasse 18, 1190 Vienna, Austria.
Core Facility Biomolecular & Cellular Analysis, BOKU University, 1190 Vienna, Austria.
Antibodies (Basel). 2025 Jun 17;14(2):50. doi: 10.3390/antib14020050.
Therapeutic antibodies with lambda light chains (λ-Abs) are underrepresented compared to kappa light chains (κ-Abs). Here, we evaluated two SARS-CoV-2-specific monoclonal antibodies (mAbs) that exhibit high (P5C3) and low (H4) antigen binding as κ and λ variants. mAbs expressed in glycoengineered did not show differences in expression levels, glycosylation, and antigen binding, while κ-Abs exhibited slightly increased thermodynamic stability over λ-Abs. SARS-CoV-2 neutralization and IgG-FcγR immune complex studies revealed increased activities of H4 IgG1κ compared to H4 IgG1λ, with no differences observed between P5C3 variants. Our results indicate that constant light chain variability and Ab specificity contribute to Ab features, a fact that should be considered in engineering therapeutics.
与kappa轻链抗体（κ-Abs）相比，带有lambda轻链的治疗性抗体（λ-Abs）的占比相对较少。在此，我们评估了两种针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的单克隆抗体（mAbs），它们作为κ和λ变体分别表现出高抗原结合能力（P5C3）和低抗原结合能力（H4）。在糖基工程中表达的单克隆抗体在表达水平、糖基化和抗原结合方面未显示出差异，而κ-Abs的热力学稳定性比λ-Abs略有提高。SARS-CoV-2中和及IgG-FcγR免疫复合物研究表明，与H4 IgG1λ相比，H4 IgG1κ的活性有所增加，而P5C3变体之间未观察到差异。我们的结果表明，恒定轻链的变异性和抗体特异性会影响抗体特性，这一事实在工程治疗中应予以考虑。
