Improving dual targeting selectivity in T-cell engagers via synapse-gated and affinity-tuned trispecific antibody design.

ABSTRACT: T-cell engagers (TCEs) represent a powerful drug modality for redirecting a patient's own T cells to recognize and eradicate cancer cells. Although TCEs have been effective in treating hematological cancers, their broad application for solid tumors has been more challenging due to the absence of tumor-specific antigens. This often leads to on-target, off-tumor toxicities and a low therapeutic index (TI). Strategies for dual-antigen targeting of double-positive cancer cells over single-positive normal tissue may improve the TI of TCEs. In this study, we report the development and characterization of a conditional dual tumor-associated antigen (TAA)-targeting trispecific antibody (TriMab) TCE composed of a non-active anchoring arm (i.e. anti-TAA1), deficient in mediating an active imm

SUBMITTER: Zhao P 

PROVIDER: S-EPMC12520116 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature