Open AccessNano-optogenetic engineering of CAR T cells for precision immunotherapy with enhanced safety
Author(s) -
Nhung Nguyen,
Kai Huang,
Hongxiang Zeng,
Jing Ji,
Rui Wang,
Shaohai Fang,
Joyce Chen,
Xin Liu,
ZhengMing Huang,
M. James You,
Anjana Rao,
Yun Huang,
Gang Han,
Yubin Zhou
Publication year - 2021
Publication title -
nature nanotechnology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 14.308
H-Index - 353
eISSN - 1748-3395
pISSN - 1748-3387
DOI - 10.1038/s41565-021-00982-5
Subject(s) - chimeric antigen receptor , optogenetics , immunotherapy , cancer research , medicine , cell therapy , photon upconversion , immune system , cell , immunology , biology , chemistry , neuroscience , genetics , ion , organic chemistry
Chimeric antigen receptor (CAR) T cell-based immunotherapy, approved by the US Food and Drug Administration, has shown curative potential in patients with haematological malignancies. However, owing to the lack of control over the location and duration of the anti-tumour immune response, CAR T cell therapy still faces safety challenges arising from cytokine release syndrome and on-target, off-tumour toxicity. Herein, we present the design of light-switchable CAR (designated LiCAR) T cells that allow real-time phototunable activation of therapeutic T cells to precisely induce tumour cell killing. When coupled with imaging-guided, surgically removable upconversion nanoplates that have enhanced near-infrared-to-blue upconversion luminescence as miniature deep-tissue photon transducers, LiCAR T cells enable both spatial and temporal control over T cell-mediated anti-tumour therapeutic activity in vivo with greatly mitigated side effects. Our nano-optogenetic immunomodulation platform not only provides a unique approach to interrogate CAR-mediated anti-tumour immunity, but also sets the stage for developing precision medicine to deliver personalized anticancer therapy.