Fig. 1: Major conventional and conditionally active T cell engager formats.
From: T cell engagers: expanding horizons in oncology and beyond
a 1+1 format comprising two single-chain variable fragments (scFvs) connected by a flexible linker. b Half-life extended 1+1 format incorporating an Fc region to prolong systemic circulation. c 2+1 format containing two tumour-binding domains and one T cell-binding domain. Alternatively, this structure could be trispecific, with each domain recognising a distinct antigen. d TCE targeting intracellular antigens, consisting of an anti-CD3 arm fused to a T cell receptor (TCR)-based domain. e Protease-activated TCE in which a masking peptide containing protease cleavage sites conceals the antigen-binding domain, enabling conditional activation. f pH-sensitive TCE with the antigen-binding domain capped by pH-responsive physiological chemicals, allowing selective activation in the acidic tumour microenvironment. g Split TCE design where the variable light (VL) and variable heavy (VH) chains of the anti-CD3 domain are separated and fused to two distinct tumour-targeting antibodies, requiring co-localisation for full activity.
