Improving the tumor selectivity of T cell engagers by logic-gated dual tumor-targeting
Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved..
Targeting single tumor antigens makes it difficult to provide sufficient tumor selectivity for T cell engagers (TCEs), leading to undesirable toxicity and even treatment failure, which is particularly serious in solid tumors. Here, we designed novel trispecific TCEs (TriTCEs) to improve the tumor selectivity of TCEs by logic-gated dual tumor-targeting. TriTCE can effectively redirect and activate T cells to kill tumor cells (∼18 pM EC50) by inducing the aggregation of dual tumor antigens, which was ∼70- or 750- fold more effective than the single tumor-targeted isotype controls, respectively. Further in vivo experiments indicated that TriTCE has the ability to accumulate in tumor tissue and can induce circulating T cells to infiltrate into tumor sites. Hence, TriTCE showed a stronger tumor growth inhibition ability and significantly prolonged the survival time of the mice. Finally, we revealed that this concept of logic-gated dual tumor-targeted TriTCE can be applied to target different tumor antigens. Cumulatively, we reported novel dual tumor-targeted TriTCEs that can mediate a robust T cell response by simultaneous recognition of dual tumor antigens at the same cell surface. TriTCEs allow better selective T cell activity on tumor cells, resulting in safer TCE treatment.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2023 |
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Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:192 |
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Enthalten in: |
Pharmacological research - 192(2023) vom: 27. Juni, Seite 106781 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Shen, Ying [VerfasserIn] |
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Links: |
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Themen: |
Antigens, Neoplasm |
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Anmerkungen: |
Date Completed 05.06.2023 Date Revised 09.06.2023 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1016/j.phrs.2023.106781 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM356232727 |
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520 | |a Targeting single tumor antigens makes it difficult to provide sufficient tumor selectivity for T cell engagers (TCEs), leading to undesirable toxicity and even treatment failure, which is particularly serious in solid tumors. Here, we designed novel trispecific TCEs (TriTCEs) to improve the tumor selectivity of TCEs by logic-gated dual tumor-targeting. TriTCE can effectively redirect and activate T cells to kill tumor cells (∼18 pM EC50) by inducing the aggregation of dual tumor antigens, which was ∼70- or 750- fold more effective than the single tumor-targeted isotype controls, respectively. Further in vivo experiments indicated that TriTCE has the ability to accumulate in tumor tissue and can induce circulating T cells to infiltrate into tumor sites. Hence, TriTCE showed a stronger tumor growth inhibition ability and significantly prolonged the survival time of the mice. Finally, we revealed that this concept of logic-gated dual tumor-targeted TriTCE can be applied to target different tumor antigens. Cumulatively, we reported novel dual tumor-targeted TriTCEs that can mediate a robust T cell response by simultaneous recognition of dual tumor antigens at the same cell surface. TriTCEs allow better selective T cell activity on tumor cells, resulting in safer TCE treatment | ||
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700 | 1 | |a Chen, Shu-Qing |e verfasserin |4 aut | |
700 | 1 | |a Zhao, Wen-Bin |e verfasserin |4 aut | |
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