High-Affinity Superantigen-Based Trifunctional Immune Cell Engager Synergizes NK and T Cell Activation for Tumor Suppression.

ABSTRACT: The development of immune cell engagers (ICEs) can be limited by logistical and functional restrictions associated with fusion protein designs, thus limiting immune cell recruitment to solid tumors. Herein, a high affinity superantigen-based multivalent ICE is developed for simultaneous activation and recruitment of NK and T cells for tumor treatment. Yeast library-based directed evolution is adopted to identify superantigen variants possessing enhanced binding affinity to immunoreceptors expressed on human T cells and NK cells. High-affinity superantigens exhibiting improved immune-stimulatory activities are then incorporated into a superantigen-based tri-functional yeast-display-enhanced multivalent immune cell engager (STYMIE), which is functionalized with a nanobody, a Neo-2/15 cytokin

SUBMITTER: Yu YA 

PROVIDER: S-EPMC11434130 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature