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Remodeling of Tumor Microenvironment by Tumor-Targeting Nanozymes Enhances Immune Activation of CAR T Cells for Combination Therapy
Zhu, Lipeng1,2; Liu, Jie1,2; Zhou, Guangyu1,2; Liu, Tzu Ming1,2; Dai, Yunlu1,2; Nie, Guangjun3; Zhao, Qi1,2
2021-08-10
Source PublicationSmall
ISSN1613-6810
Volume17Issue:43Pages:2102624
Abstract

Targeting B7-H3 chimeric antigen receptor (CAR) T cells has antitumor potential for therapy of non-small cell lung cancer (NSCLC) in preclinical studies. However, CAR T cell therapy remains a formidable challenge for the treatment of solid tumors due to the heterogeneous and immunosuppressive tumor microenvironment (TME). Nanozymes exhibit merits modulating the immunosuppression of the tumor milieu. Here, a synergetic strategy by combination of nanozymes and CAR T cells in solid tumors is described. This nanozyme with dual photothermal-nanocatalytic properties is endowed to remodel TME by destroying its compact structure. It is found that the B7-H3 CAR T cells infused in mice engrafted with the NSCLC cells have superior antitumor activity after nanozyme ablation of the tumor. Importantly, it is found that the changes altered immune-hostile cancer environment, resulting in enhanced activation and infiltration of B7-H3 CAR T cells. The first evidence that the process of combination nanozyme therapy effectively improves the therapeutic index of CAR T cells is presented. Thus, this study clearly supports that the TME-immunomodulated nanozyme is a promising tool to improve the therapeutic obstacles of CAR T cells against solid tumors.

KeywordB7-h3 Immune Checkpoint Chimeric Antigen Receptor t Cell Immunotherapy Nanozyme Photothermal-nanocatalytic Effect
DOI10.1002/smll.202102624
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaChemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
WOS SubjectChemistry, Multidisciplinary ; Chemistry, Physical ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary ; Physics, Applied ; Physics, Condensed Matter
WOS IDWOS:000683607300001
Scopus ID2-s2.0-85112110337
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Document TypeJournal article
CollectionMinistry of Education Frontiers Science Center for Precision Oncology, University of Macau
Faculty of Health Sciences
Cancer Centre
Institute of Translational Medicine
Corresponding AuthorZhao, Qi
Affiliation1.Cancer Centre, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, 999078, Macao
2.MoE Frontiers Science Center for Precision Oncology, University of Macau, 999078, Macao
3.CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience and Technology, Beijing, 100190, China
First Author AffilicationCancer Centre;  University of Macau
Corresponding Author AffilicationCancer Centre;  University of Macau
Recommended Citation
GB/T 7714
Zhu, Lipeng,Liu, Jie,Zhou, Guangyu,et al. Remodeling of Tumor Microenvironment by Tumor-Targeting Nanozymes Enhances Immune Activation of CAR T Cells for Combination Therapy[J]. Small, 2021, 17(43), 2102624.
APA Zhu, Lipeng., Liu, Jie., Zhou, Guangyu., Liu, Tzu Ming., Dai, Yunlu., Nie, Guangjun., & Zhao, Qi (2021). Remodeling of Tumor Microenvironment by Tumor-Targeting Nanozymes Enhances Immune Activation of CAR T Cells for Combination Therapy. Small, 17(43), 2102624.
MLA Zhu, Lipeng,et al."Remodeling of Tumor Microenvironment by Tumor-Targeting Nanozymes Enhances Immune Activation of CAR T Cells for Combination Therapy".Small 17.43(2021):2102624.
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