دورية أكاديمية
أعرض في EDS

A CSF-1R-blocking antibody/IL-10 fusion protein increases anti-tumor immunity by effectuating tumor-resident CD8 + T cells.

التفاصيل البيبلوغرافية
العنوان: A CSF-1R-blocking antibody/IL-10 fusion protein increases anti-tumor immunity by effectuating tumor-resident CD8 + T cells.
المؤلفون: Chang YW; Cancer and Immunology Research Center, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan., Hsiao HW; Elixiron Immunotherapeutics (Hong Kong) Ltd., Hong Kong., Chen JP; Cancer and Immunology Research Center, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan., Tzeng SF; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11221, Taiwan., Tsai CH; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11221, Taiwan., Wu CY; Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan., Hsieh HH; Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan., Carmona SJ; Department of Oncology, University of Lausanne, Lausanne, Switzerland; Ludwig Institute for Cancer Research at University of Lausanne, Lausanne, Switzerland., Andreatta M; Department of Oncology, University of Lausanne, Lausanne, Switzerland; Ludwig Institute for Cancer Research at University of Lausanne, Lausanne, Switzerland., Di Conza G; Department of Oncology, University of Lausanne, Lausanne, Switzerland; Ludwig Institute for Cancer Research at University of Lausanne, Lausanne, Switzerland., Su MT; Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan., Koni PA; Elixiron Immunotherapeutics (Hong Kong) Ltd., Hong Kong., Ho PC; Department of Oncology, University of Lausanne, Lausanne, Switzerland; Ludwig Institute for Cancer Research at University of Lausanne, Lausanne, Switzerland., Chen HK; Elixiron Immunotherapeutics (Hong Kong) Ltd., Hong Kong. Electronic address: hkchen@elixiron.com., Yang MH; Cancer and Immunology Research Center, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan; Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan; Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan; Department of Oncology, Taipei Veterans General Hospital, Taipei 11217, Taiwan; Department of Teaching and Research, Taipei City Hospital, Taipei, Taiwan. Electronic address: mhyang2@nycu.edu.tw.
المصدر: Cell reports. Medicine [Cell Rep Med] 2023 Aug 15; Vol. 4 (8), pp. 101154.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101766894 Publication Model: Print Cited Medium: Internet ISSN: 2666-3791 (Electronic) Linking ISSN: 26663791 NLM ISO Abbreviation: Cell Rep Med Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Cambridge, MA] : Cell Press, [2020]-
مواضيع طبية MeSH: Neoplasms*/pathology , Antineoplastic Agents*/pharmacology, Humans ; CD8-Positive T-Lymphocytes ; Interleukin-10/metabolism ; Receptor Protein-Tyrosine Kinases/metabolism ; Receptors, Colony-Stimulating Factor/metabolism ; Tumor Microenvironment
مستخلص: Strategies to increase intratumoral concentrations of an anticancer agent are desirable to optimize its therapeutic potential when said agent is efficacious primarily within a tumor but also have significant systemic side effects. Here, we generate a bifunctional protein by fusing interleukin-10 (IL-10) to a colony-stimulating factor-1 receptor (CSF-1R)-blocking antibody. The fusion protein demonstrates significant antitumor activity in multiple cancer models, especially head and neck cancer. Moreover, this bifunctional protein not only leads to the anticipated reduction in tumor-associated macrophages but also triggers proliferation, activation, and metabolic reprogramming of CD8 + T cells. Furthermore, it extends the clonotype diversity of tumor-infiltrated T cells and shifts the tumor microenvironment (TME) to an immune-active state. This study suggests an efficient strategy for designing immunotherapeutic agents by fusing a potent immunostimulatory molecule to an antibody targeting TME-enriched factors.
Competing Interests: Declaration of interests P.-C.H. is a scientific advisor for Elixiron Immunotherapeutics, Acepodia, and Novartis and is a cofounder of Pilatus Biosciences. P.-C.H. received research support from Elixiron Immunotherapeutics. P.-C.H. also received research support from Roche.
(Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
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فهرسة مساهمة: Keywords: CD8 T cell; TCR repertoire; colony-stimulating factor 1-receptor; head and neck cancer; immunotherapy; interleukin-10; macrophage; tumor microenvironment
المشرفين على المادة: 130068-27-8 (Interleukin-10)
0 (Antineoplastic Agents)
EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
0 (Receptors, Colony-Stimulating Factor)
تواريخ الأحداث: Date Created: 20230816 Date Completed: 20230818 Latest Revision: 20230823
رمز التحديث: 20230823
مُعرف محوري في PubMed: PMC10439276
DOI: 10.1016/j.xcrm.2023.101154
PMID: 37586318
قاعدة البيانات: MEDLINE
الوصف
تدمد:2666-3791
DOI:10.1016/j.xcrm.2023.101154