Optogenetic-controlled immunotherapeutic designer cells for post-surgical cancer immunotherapy

Yuanhuan Yu, Xin Wu, Meiyan Wang, Wenjing Liu, Li Zhang, Ying Zhang, Zhilin Hu, Xuantong Zhou, Wenzheng Jiang, Qiang Zou, Fengfeng Cai () and Haifeng Ye ()
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Yuanhuan Yu: East China Normal University
Xin Wu: East China Normal University
Meiyan Wang: East China Normal University
Wenjing Liu: East China Normal University
Li Zhang: East China Normal University
Ying Zhang: East China Normal University
Zhilin Hu: Shanghai Jiao Tong University School of Medicine
Xuantong Zhou: East China Normal University
Wenzheng Jiang: East China Normal University
Qiang Zou: Shanghai Jiao Tong University School of Medicine
Fengfeng Cai: Tongji University
Haifeng Ye: East China Normal University

Nature Communications, 2022, vol. 13, issue 1, 1-14

Abstract: Abstract Surgical resection is the main treatment option for most solid tumors, yet cancer recurrence after surgical resection remains a significant challenge in cancer therapy. Recent advances in cancer immunotherapy are enabling radical cures for many tumor patients, but these technologies remain challenging to apply because of side effects related to uncontrollable immune system activation. Here, we develop far-red light-controlled immunomodulatory engineered cells (FLICs) that we load into a hydrogel scaffold, enabling the precise optogenetic control of cytokines release (IFN-β, TNF-α, and IL-12) upon illumination. Experiments with a B16F10 melanoma resection mouse model show that FLICs-loaded hydrogel implants placed at the surgical wound site achieve sustainable release of immunomodulatory cytokines, leading to prevention of tumor recurrence and increased animal survival. Moreover, the FLICs-loaded hydrogel implants elicit long-term immunological memory that prevents against tumor recurrence. Our findings illustrate that this optogenetic perioperative immunotherapy with FLICs-loaded hydrogel implants offers a safe treatment option for solid tumors based on activating host innate and adaptive immune systems to inhibit tumor recurrence after surgery. Beyond extending the optogenetics toolbox for immunotherapy, we envision that our optogenetic-controlled living cell factory platform could be deployed for other biomedical contexts requiring precision induction of bio-therapeutic dosage.

Date: 2022
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DOI: 10.1038/s41467-022-33891-9

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