Novel strategy for tumor immunotherapy using FITC-folate bispecific adapter bridged CAR immune cell cocktails
Adoptive immune cell-based therapies have shown promise in cancer treatment, yet their efficacy against solid tumors is often limited by the immunosuppressive tumor microenvironment (TME). To overcome these barriers, we design an innovative immune cell cocktail as a combinatorial biomaterial platfor...
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KeAi Communications Co., Ltd.
2025-10-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X25002531 |
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| author | Bin Liu Jingqiao Shen Yunhan Wu Chun Fai Wong Tran Yin Hei Johnny Wen-tao Li Sydney N. Hummel Gyuhyung Jin Nathan R. Petrucci Dan Michelle Wang Xiaoping Bao Cheng Dong Yun Chang |
| author_facet | Bin Liu Jingqiao Shen Yunhan Wu Chun Fai Wong Tran Yin Hei Johnny Wen-tao Li Sydney N. Hummel Gyuhyung Jin Nathan R. Petrucci Dan Michelle Wang Xiaoping Bao Cheng Dong Yun Chang |
| author_sort | Bin Liu |
| collection | DOAJ |
| description | Adoptive immune cell-based therapies have shown promise in cancer treatment, yet their efficacy against solid tumors is often limited by the immunosuppressive tumor microenvironment (TME). To overcome these barriers, we design an innovative immune cell cocktail as a combinatorial biomaterial platform, which harnessing the complementary functions of neutrophils and natural killer (NK) cells derived from human pluripotent stem cells (hPSCs). Using CRISPR/Cas9, we introduce an anti-fluorescein isothiocyanate (FITC) chimeric antigen receptor (CAR) construct into the AAVS1 safe harbor locus of hPSCs, allowing for the differentiation of CAR-modified neutrophils and NK cells. These CAR neutrophils exhibit robust anti-tumor activity, forming immune synapses with tumor cells tagged via a bispecific adapter (FITC-folate), even in hypoxic TMEs, while CAR NK cells demonstrate antigen-specific cytotoxicity. Together, the cocktail biomaterial composed of CAR neutrophils and CAR NK cells creates a synergistic anti-tumor effect: having neutrophils enhance TME modulation, and NK cells provide targeted cytotoxicity. This biomaterial offers a scalable and off-the-shelf solution for producing CAR neutrophils and CAR NK cells, potentially reducing needs for high-dose exogenous cytokines and minimizing immune-related toxicities. Our findings suggest that hPSC-derived CAR neutrophils and CAR NK cells may form an effective immuno-cocktail biomaterial, offering a feasible strategy for advancing solid tumor immunotherapy through cellular synergy and TME adaptation. |
| format | Article |
| id | doaj-art-2a0d7e1e74ea44eaa3dad600b691803f |
| institution | Kabale University |
| issn | 2452-199X |
| language | English |
| publishDate | 2025-10-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj-art-2a0d7e1e74ea44eaa3dad600b691803f2025-08-24T05:13:47ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-10-015252954010.1016/j.bioactmat.2025.06.025Novel strategy for tumor immunotherapy using FITC-folate bispecific adapter bridged CAR immune cell cocktailsBin Liu0Jingqiao Shen1Yunhan Wu2Chun Fai Wong3Tran Yin Hei4Johnny Wen-tao Li5Sydney N. Hummel6Gyuhyung Jin7Nathan R. Petrucci8Dan Michelle Wang9Xiaoping Bao10Cheng Dong11Yun Chang12Department of Biomedical Engineering, The Hong Kong Polytechnic University, 999077, Hong Kong, China; The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, 518000, ChinaDavidson School of Chemical Engineering, Purdue University, West Lafayette, IN, 47907, USA; Purdue University Institute for Cancer Research, West Lafayette, IN, 47907, USADepartment of Biomedical Engineering, The Hong Kong Polytechnic University, 999077, Hong Kong, ChinaDepartment of Biomedical Engineering, The Hong Kong Polytechnic University, 999077, Hong Kong, ChinaDepartment of Biomedical Engineering, The Hong Kong Polytechnic University, 999077, Hong Kong, ChinaDepartment of Biomedical Engineering, The Hong Kong Polytechnic University, 999077, Hong Kong, ChinaDavidson School of Chemical Engineering, Purdue University, West Lafayette, IN, 47907, USA; Purdue University Institute for Cancer Research, West Lafayette, IN, 47907, USADavidson School of Chemical Engineering, Purdue University, West Lafayette, IN, 47907, USA; Purdue University Institute for Cancer Research, West Lafayette, IN, 47907, USADavidson School of Chemical Engineering, Purdue University, West Lafayette, IN, 47907, USA; Purdue University Institute for Cancer Research, West Lafayette, IN, 47907, USASchool of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, 999077, Hong Kong, ChinaDavidson School of Chemical Engineering, Purdue University, West Lafayette, IN, 47907, USA; Purdue University Institute for Cancer Research, West Lafayette, IN, 47907, USA; Corresponding author. Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN, 47907, USADepartment of Biomedical Engineering, The Hong Kong Polytechnic University, 999077, Hong Kong, China; The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, 518000, China; Corresponding author. Department of Biomedical Engineering, The Hong Kong Polytechnic University, 999077, Hong Kong, ChinaDepartment of Biomedical Engineering, The Hong Kong Polytechnic University, 999077, Hong Kong, China; The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, 518000, China; Corresponding author. Department of Biomedical Engineering, The Hong Kong Polytechnic University, 999077, Hong Kong, ChinaAdoptive immune cell-based therapies have shown promise in cancer treatment, yet their efficacy against solid tumors is often limited by the immunosuppressive tumor microenvironment (TME). To overcome these barriers, we design an innovative immune cell cocktail as a combinatorial biomaterial platform, which harnessing the complementary functions of neutrophils and natural killer (NK) cells derived from human pluripotent stem cells (hPSCs). Using CRISPR/Cas9, we introduce an anti-fluorescein isothiocyanate (FITC) chimeric antigen receptor (CAR) construct into the AAVS1 safe harbor locus of hPSCs, allowing for the differentiation of CAR-modified neutrophils and NK cells. These CAR neutrophils exhibit robust anti-tumor activity, forming immune synapses with tumor cells tagged via a bispecific adapter (FITC-folate), even in hypoxic TMEs, while CAR NK cells demonstrate antigen-specific cytotoxicity. Together, the cocktail biomaterial composed of CAR neutrophils and CAR NK cells creates a synergistic anti-tumor effect: having neutrophils enhance TME modulation, and NK cells provide targeted cytotoxicity. This biomaterial offers a scalable and off-the-shelf solution for producing CAR neutrophils and CAR NK cells, potentially reducing needs for high-dose exogenous cytokines and minimizing immune-related toxicities. Our findings suggest that hPSC-derived CAR neutrophils and CAR NK cells may form an effective immuno-cocktail biomaterial, offering a feasible strategy for advancing solid tumor immunotherapy through cellular synergy and TME adaptation.http://www.sciencedirect.com/science/article/pii/S2452199X25002531Human pluripotent stem cellsNeutrophilsNatural killer cellsCocktail biomaterialBispecific adapter |
| spellingShingle | Bin Liu Jingqiao Shen Yunhan Wu Chun Fai Wong Tran Yin Hei Johnny Wen-tao Li Sydney N. Hummel Gyuhyung Jin Nathan R. Petrucci Dan Michelle Wang Xiaoping Bao Cheng Dong Yun Chang Novel strategy for tumor immunotherapy using FITC-folate bispecific adapter bridged CAR immune cell cocktails Bioactive Materials Human pluripotent stem cells Neutrophils Natural killer cells Cocktail biomaterial Bispecific adapter |
| title | Novel strategy for tumor immunotherapy using FITC-folate bispecific adapter bridged CAR immune cell cocktails |
| title_full | Novel strategy for tumor immunotherapy using FITC-folate bispecific adapter bridged CAR immune cell cocktails |
| title_fullStr | Novel strategy for tumor immunotherapy using FITC-folate bispecific adapter bridged CAR immune cell cocktails |
| title_full_unstemmed | Novel strategy for tumor immunotherapy using FITC-folate bispecific adapter bridged CAR immune cell cocktails |
| title_short | Novel strategy for tumor immunotherapy using FITC-folate bispecific adapter bridged CAR immune cell cocktails |
| title_sort | novel strategy for tumor immunotherapy using fitc folate bispecific adapter bridged car immune cell cocktails |
| topic | Human pluripotent stem cells Neutrophils Natural killer cells Cocktail biomaterial Bispecific adapter |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X25002531 |
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