Researchers at Queen Mary University of London in the United Kingdom analyze the strengths, weaknesses, opportunities, and threats (SWOT) of bispecific T-cell engagers (BiTEs) in a review article published in March in Anticancer Research.
Superior anti-tumor efficacy compared with monoclonal antibodies and other bispecific antibodies is a strength of BiTEs, Kathrine S. Rallis, MSc, and colleagues write. “Targeting two pathways improves efficacy and resistance,” they observe. Another strength is a lack of major histocompatibility complex (MHC) and human leukocyte antigen (HLA) restriction, allowing for universal off-the-shelf use.
Rare but severe toxicities (specifically, severe cytokine release syndrome and neurotoxicity) and relapse and resistance are BiTEs’ principal weaknesses, they write. Moreover, despite the superior anti-tumor efficacy of BiTEs compared with other antibody constructs, costly initial synthesis and competitive licensing have restricted their use.
With over 100 known bispecific antibody formats, a quarter of which are in therapeutic development, new antigen targets present an opportunity for BiTEs. However, numerous unsuccessful attempts to translate agents to the clinic are a weakness. Other designs, such as dual-affinity re-targeting, have gained interest, while adoptive cell therapies threaten the sustainability of BiTEs.
- Rallis KS, Hillyar CRT, Sideris M, Davies JK. T-cell-based Immunotherapies for Haematological Cancers, Part A: A SWOT Analysis of Immune Checkpoint Inhibitors (ICIs) and Bispecific T-Cell Engagers (BiTEs). Anticancer Res. 2021;41(3):1123-1141. doi:10.21873/anticanres.14870