Premium
Nanoengineered CAR‐T Biohybrids for Solid Tumor Immunotherapy with Microenvironment Photothermal‐Remodeling Strategy
Author(s) -
Chen Ze,
Pan Hong,
Luo Yingmei,
Yin Ting,
Zhang Baozhen,
Liao Jianhong,
Wang Mengmeng,
Tang Xiaofan,
Huang Guojun,
Deng Guanjun,
Zheng Mingbin,
Cai Lintao
Publication year - 2021
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.202007494
Subject(s) - tumor microenvironment , immunotherapy , chimeric antigen receptor , cancer research , photothermal therapy , extracellular matrix , materials science , immune system , cancer immunotherapy , chemistry , medicine , immunology , nanotechnology , microbiology and biotechnology , biology
Abstract Chimeric antigen receptor T cell (CAR‐T) therapy has shown remarkable clinical success in eradicating hematologic malignancies. However, hostile microenvironment in solid tumors severely prevents CAR‐T cells migrating, infiltrating, and killing. Herein, a nanoengineered CAR‐T strategy is reported for enhancing solid tumor therapy through bioorthogonal conjugation with a nano‐photosensitizer (indocyanine green nanoparticles, INPs) as a microenvironment modulator. INPs engineered CAR‐T biohybrids (CT‐INPs) not only retain the original activities and functions of CAR‐T cells, but it is further armed with fluorescent tracing and microenvironment remodeling abilities. Irradiated with laser, CT‐INPs demonstrate that mild photothermal intervention destroys the extracellular matrix, expanded blood vessels, loosened compact tissue, and stimulated chemokine secretion without damping CAR‐T cell activities. Those regulations induce an immune‐favorable tumor microenvironment for recruitment and infiltration of CT‐INPs. CT‐INPs triggered photothermal effects collapse the physical and immunological barriers of solid tumor, and robustly boosted CAR‐T immunotherapy. Therefore, CAR‐T biohybrids provide reliable treatment strategy for solid tumor immunotherapy via microenvironment reconstruction.