Bioconjugated liquid-like solid enhances characterization of solid tumor - chimeric antigen receptor T cell interactions
- PMID: 37788737
- DOI: 10.1016/j.actbio.2023.09.042
Bioconjugated liquid-like solid enhances characterization of solid tumor - chimeric antigen receptor T cell interactions
Abstract
Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable success as an immunotherapy for hematological malignancies, and its potential for treating solid tumors is an active area of research. However, limited trafficking and mobility of T cells within the tumor microenvironment (TME) present challenges for CAR T cell therapy in solid tumors. To gain a better understanding of CAR T cell function in solid tumors, we subjected CD70-specific CAR T cells to a challenge by evaluating their immune trafficking and infiltration through a confined 3D microchannel network in a bio-conjugated liquid-like solid (LLS) medium. Our results demonstrated successful CAR T cell migration and anti-tumor activity against CD70-expressing glioblastoma and osteosarcoma tumors. Through comprehensive analysis of cytokines and chemokines, combined with in situ imaging, we elucidated that immune recruitment occurred via chemotaxis, and the effector-to-target ratio plays an important role in overall antitumor function. Furthermore, through single-cell collection and transcriptomic profiling, we identified differential gene expression among the immune subpopulations. Our findings provide valuable insights into the complex dynamics of CAR T cell function in solid tumors, informing future research and development in this promising cancer treatment approach. STATEMENT OF SIGNIFICANCE: The use of specialized immune cells named CAR T cells to combat cancers has demonstrated remarkable success against blood cancers. However, this success is not replicated in solid tumors, such as brain or bone cancers, mainly due to the physical barriers of these solid tumors. Currently, preclinical technologies do not allow for reliable evaluation of tumor-immune cell interactions. To better study these specialized CAR T cells, we have developed an innovative in vitro three-dimensional model that promises to dissect the interactions between tumors and CAR T cells at the single-cell level. Our findings provide valuable insights into the complex dynamics of CAR T cell function in solid tumors, informing future research and development in this promising cancer treatment approach.
Keywords: CAR T trafficking; Cancer; Chimeric antigen receptor (CAR) T cell; Cytotoxicity; Liquid-like solid.
Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Conflict of interest statement
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Update of
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Three-Dimensional Bioconjugated Liquid-Like Solid (LLS) Enhance Characterization of Solid Tumor - Chimeric Antigen Receptor T cell interactions.bioRxiv [Preprint]. 2023 Feb 21:2023.02.17.529033. doi: 10.1101/2023.02.17.529033. bioRxiv. 2023. Update in: Acta Biomater. 2023 Dec;172:466-479. doi: 10.1016/j.actbio.2023.09.042. PMID: 36865164 Free PMC article. Updated. Preprint.
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Three-Dimensional Bioconjugated Liquid-Like Solid (LLS) Enhance Characterization of Solid Tumor - Chimeric Antigen Receptor T cell interactions.bioRxiv [Preprint]. 2023 Feb 21:2023.02.17.529033. doi: 10.1101/2023.02.17.529033. bioRxiv. 2023. Update in: Acta Biomater. 2023 Dec;172:466-479. doi: 10.1016/j.actbio.2023.09.042. PMID: 36865164 Free PMC article. Updated. Preprint.
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