Cytotherapy · 2026
Yeast surface display meets immunotherapy: unlocking the potential of T cells.
СтатьяОбзорНазвание и аннотация: Перевод в очереди
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Wang Jie, Li Yukun, Shi Jinglong, Yao Zhouchi, Yuan Ping, Li Sizhe, Wang Hong, Chen Guodong, He Weiguo, Wu Daichao
Аннотация
BACKGROUND AIMS: While T-cell receptors (TCRs) hold immense therapeutic potential, their clinical translation is bottlenecked by the scarcity of high-affinity, specific clones and the instability of recombinant formats. Existing display technologies fall short: phage display often fails to produce properly folded TCRs, and mammalian display is low-throughput. This review is the first to comprehensively synthesize how yeast surface display (YSD) is uniquely positioned to overcome these hurdles and build a new pipeline for TCR based drug discovery.
METHODS: We articulate how YSD's eukaryotic machinery enables the robust expression and engineering of complex TCRs and peptide-MHC (pMHC) libraries. We then critically catalog and evaluate pioneering strategies where YSD has been used to evolve TCRs with enhanced affinity and stability while minimizing cross-reactivity and discover novel antigenic targets through unbiased library-to-library screening.
RESULTS: By mapping this largely pre-clinical landscape, our work establishes a foundational framework that bridges fundamental protein engineering with future therapeutic applications.
CONCLUSIONS: We conclude by outlining a translational roadmap, arguing that YSD derived molecules are poised to become the cornerstone of safer, more effective, and personalized T-cell therapies.
METHODS: We articulate how YSD's eukaryotic machinery enables the robust expression and engineering of complex TCRs and peptide-MHC (pMHC) libraries. We then critically catalog and evaluate pioneering strategies where YSD has been used to evolve TCRs with enhanced affinity and stability while minimizing cross-reactivity and discover novel antigenic targets through unbiased library-to-library screening.
RESULTS: By mapping this largely pre-clinical landscape, our work establishes a foundational framework that bridges fundamental protein engineering with future therapeutic applications.
CONCLUSIONS: We conclude by outlining a translational roadmap, arguing that YSD derived molecules are poised to become the cornerstone of safer, more effective, and personalized T-cell therapies.