ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
High-Affinity Superantigen-Based Trifunctional Immune Cell Engager Synergizes NK and T Cell Activation for Tumor Suppression.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Superantigens in Cancer Immunotherapy: Mechanisms, Engineering Strategies, and Therapeutic Potential.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Advancing immunotherapy via multiple immune cells co-engagement.Frontiers in immunology · 2026Review
- Nanobodies and their derivatives: pioneering the future of cancer immunotherapy.Cell communication and signaling : CCS · 2025Review
- High-Affinity Superantigen-Based Trifunctional Immune Cell Engager Synergizes NK and T Cell Activation for Tumor Suppression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
Corrections and comments
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Authors and funding
8 authors.
Funding
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 cytokine, and an Fc domain for tumor targeting, immune stimulation, and prolonged circulation, respectively. Intravenous administration of STYMIE enhances NK and T cell recruitment into solid tumors, leading to enhanced inhibition in multiple tumor models. The study offers design principles for multifunctional ICEs.
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Registered trials
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