Monoclonal antibodies (mAbs) enjoy numerous therapeutic applications due to their ability to engage specific antigens on cell surfaces. Since native (homodimeric) mAbs as such have limited applications in therapy due to the absence of a curing agent, different formats of antibodies have been developed for various therapeutic applications. As of 2023, 145 mAb-based drugs have been approved by the United States Food and Drug Administration (US FDA). 9 Of these, eleven bispecific antibodies have been marketed in the US. Among them, T cell engaging constructs form the largest class in clinical pipeline with eight bispecific T cell engagers in market for cancer treatment. T cell engagers are antibody-based therapeutics that simultaneously engage CD3 receptor on the T cell and a tumor-associated antigen. Different formats of T cell engagers have been developed, like diabody, CrossMab, BiTE, dual affinity retargeting antibodies (DART), tandem diabody (TandAb), synthetic bispecific mAbs (SynAbs), checkpoint inhibitory T cell engagers (CiTEs) and more recently bispecific antibody constructs (bsAcs). Similar to the first FDA-approved bispecific construct blinatumomab, most of these formats are based on or derived from small fragment antigenbinding regions (Fabs, typically 50-60 kDa). Due to their size, fragment-based bispecifics suffer from short half-life and require continuous infusion. This is less the case for IgG-like bispecifics, such as mosunetuzumab, which offer higher stability and longer serum half-life. Besides classical biosynthesis of bispecifics via recombinant expression, evolution of bio-orthogonal (click) chemistry has led to the development of antibody conjugates produced by synthetic methods, also using native mAbs. In this approach, strain-promoted azide alkyne cycloaddition (SPAAC), inverse electron-demand Diels-Alder (IEDDA) reaction between a strained alkene/alkyne and tetrazine, and alkyne strain-promoted oxidationcontrolled ortho-quinone (SPOCQ) cycloaddition have been successfully employed to develop antibody conjugates. The modularity of this approach offers late-stage combination of Fabs, which may be appealing for screening Fab-mAb combinations prior to upscaling and production. Herein, we report a convenient approach in which our biogenic tyrosine-based click reaction between an oxidized tyrosine and a BCN handle is used to prepare 2:1 HER2×CD3 T cell-dependent bispecific antibody construct. Due to the homodemeric nature of native antibodies, such a 2:1 platform is less conveniently accessible than a 2:2 conjugate, although methods of heterodimerization of antibodies have also proven useful for the preparation of 2:1 bispecifics. With a construct that displays bivalency for the tumor-associated antigen (TAA) and monovalent binding to T cells, preferential T cell activation at tumor cells over healthy cells can be retained. Specifically, it can be expected that monovalent binding to the T cell associated CD3 receptor aids in avoiding CD3 activation in the absence of TAA. As such, we present an approach for the convenient conversion of antibodies with C-terminally placed G4Y tag on light chains into a IgG-like 2:1 TDBA via a few chemical and chemoenzymatic steps.