T Cell Engager (TCE) based Bispecific Antibody (BsAb) Design Service

Leveraging the cytotoxic potential of immune cells, particularly T cells, to augment anti-tumor responses has emerged as a promising approach in the management of cancer. Recently developed bispecific antibodies (BsAbs), notably bispecific T cell engagers (BiTEs), have accelerated the evolution of immunotherapeutic strategies by redirecting T cells toward malignant cells. Based on these, Creative Biolabs offers a specialized T Cell Engager (TCE)-based BsAb Design Service, facilitating investigation for our customers into solid tumor therapies.

Fig.1 Schematic depiction of the architecture and functional mechanism of a prototypical bispecific T-cell engager.^{1, 3}

Structures of TCE-Based BsAbs Design

Leveraging the IgG architecture, BsAbs modeled on this framework exhibit a structure reminiscent of native immunoglobulins. The predominant approach to generating IgG-based BsAbs involves reassembling half-molecules obtained from distinct parental antibodies. Various strategies offered in our one-stop BsAb development platform—such as engineered orthogonal Fab interfaces and the knobs-into-holes (KIH) method, among others—have further refined the assembly of functional half-molecule constituents.

Based on their structural attributes, BsAbs are categorized into two main classes: those based on IgG and those constructed from variable fragment (Fv) elements, the latter typically possessing brief half-lives that require continuous administration. Alongside the BiTE format, platforms such as single-chain diabodies, dual-affinity retargeting antibodies (DARTs), and tandem diabodies (TandAbs) have been developed for the production of Fv-based BsAbs.

Hot Targets of TCE-Based BsAbs Design

TCE-based bispecific antibodies are engineered molecules integrating binding sites for both the T cell receptor (TCR) and tumor-associated or tumor-specific antigens, thereby conferring dual antigen specificity in a single construct. Among these, CD3-targeted antibodies are particularly prominent in cancer immunotherapy, as they reinforce TCR structural integrity and promote the signal transmission required for T cell activation. Antibodies against CD3 may either stimulate or dampen T cell signaling, influencing effector cell elimination or inducing a regulatory phenotype. Creative Biolabs offers a diverse portfolio of CD3 BsAbs.

Published Data

Fig.2 BsAb-facilitated T-cell and tumor cell interaction initiates chemotactic signaling for additional T-cell recruitment.^{2. 3}

BsAbs targeting the CD3 T-cell receptor (TCR) and a tumor-associated antigen (TAA) can recruit T-cells to tumor sites, forming an immune synapse analogous to natural TCR-MHC/TAA interactions. Clinical investigations have demonstrated the efficacy of CD3xTAA BsAbs in treating non-Hodgkin's lymphoma and acute lymphoblastic leukemia. Researchers evaluated CD3xHER2 BsAbs in breast cancer tumoroid arrays with healthy donor-derived T-cells, finding that initial BsAb-mediated T-cell-tumor interactions induced chemotactic recruitment of additional T-cells, essential for effective tumoroid destruction.

Creative Biolabs boasts a highly skilled research team specializing in BsAbs, supported by advanced engineering platforms. We offer customized TCE-based BsAbs development services that encompass design, engineering, production, and comprehensive analysis.