2. Academic Validation
  3. Nanoengineered CAR-T Biohybrids for Solid Tumor Immunotherapy with Microenvironment Photothermal-Remodeling Strategy

Nanoengineered CAR-T Biohybrids for Solid Tumor Immunotherapy with Microenvironment Photothermal-Remodeling Strategy

  • Small. 2021 Apr;17(14):e2007494. doi: 10.1002/smll.202007494.
Ze Chen 1,  Hong Pan 1,  Yingmei Luo 2,  Ting Yin 2,  Baozhen Zhang 1,  Jianhong Liao 1,  Mengmeng Wang 1,  Xiaofan Tang 1,  Guojun Huang 1,  Guanjun Deng 1,  Mingbin Zheng 1 2 3 4,  Lintao Cai 1 4
Affiliations

Affiliations

  • 1 Guangdong Key Laboratory of Nanomedicine, CAS-HK Joint Lab for Biomaterials, Shenzhen Engineering Laboratory of Nanomedicine and Nanoformulations, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen, 518055, China.
  • 2 Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Dongguan, 523808, China.
  • 3 National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, Southern University of Science and Technology, Shenzhen, 518112, China.
  • 4 Medical Device Research and Development Center, Zhuhai Institute of Advanced Technology Chinese Academy of Sciences, Zhuhai, 519000, China.
PMID: 33711191 DOI: 10.1002/smll.202007494
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.

Keywords

bioactive material; chimeric antigen receptor T cell therapy; microenvironment remodeling; physiologic barrier; solid tumor.

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