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

• Published in: Nature communications Vol. 13; no. 1; p. 6357
• Main Authors: Yu, Yuanhuan, Wu, Xin, Wang, Meiyan, Liu, Wenjing, Zhang, Li, Zhang, Ying, Hu, Zhilin, Zhou, Xuantong, Jiang, Wenzheng, Zou, Qiang, Cai, Fengfeng, Ye, Haifeng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26-10-2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13/107; 13/21; 13/44; 38/39; 631/154/152; 631/1647/2253; 631/1647/338/552; 631/61/51/1844; 96/10; Adaptive systems; Animal models; Animals; Cancer; Cancer immunotherapy; Cytokines; Genetics; Humanities and Social Sciences; Hydrogels; Immune system; Immunologic Factors; Immunological memory; Immunology; Immunomodulation; Immunosurveillance; Immunotherapy; Implants; Information processing; Interleukin 12; Interleukin-12 - genetics; Melanoma; Mesenchyme; Mice; multidisciplinary; Neoplasm Recurrence, Local; Optics; Optogenetics; Scaffolds; Science; Science (multidisciplinary); Side effects; Solid tumors; Stem cell transplantation; Stem cells; Surgery; Tumor Necrosis Factor-alpha; Tumor necrosis factor-α; Tumors; β-Interferon
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-33891-9

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.
The induction of long-term systemic immunosurveillance can protect against post-surgery tumor recurrence. Here the authors describe the design of optogenetic-controlled cytokine secreting (IFN-β, TNF-α, and IL-12) engineered mesenchymal stem cells loaded into a hydrogel scaffold, eliciting long-term immune memory and preventing post-operative recurrence in preclinical cancer models.