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Engineered extracellular vesicles for concurrent Anti-PDL1 immunotherapy and chemotherapy.
Chen, Yundi; Wang, Lixue; Zheng, Mingfeng; Zhu, Chuandong; Wang, Guosheng; Xia, Yiqiu; Blumenthal, Ethan J; Mao, Wenjun; Wan, Yuan.
Affiliation
  • Chen Y; The Pq Laboratory of Micro/Nano BiomeDx, Department of Biomedical Engineering, Binghamton University-SUNY, Binghamton, NY, 13902, United States.
  • Wang L; The Pq Laboratory of Micro/Nano BiomeDx, Department of Biomedical Engineering, Binghamton University-SUNY, Binghamton, NY, 13902, United States.
  • Zheng M; Department of Radiotherapy, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210003, China.
  • Zhu C; Department of Cardiothoracic Surgery, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, 214023, China.
  • Wang G; The Pq Laboratory of Micro/Nano BiomeDx, Department of Biomedical Engineering, Binghamton University-SUNY, Binghamton, NY, 13902, United States.
  • Xia Y; Department of Radiotherapy, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210003, China.
  • Blumenthal EJ; The Pq Laboratory of Micro/Nano BiomeDx, Department of Biomedical Engineering, Binghamton University-SUNY, Binghamton, NY, 13902, United States.
  • Mao W; Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA, 15213, United States.
  • Wan Y; The Pq Laboratory of Micro/Nano BiomeDx, Department of Biomedical Engineering, Binghamton University-SUNY, Binghamton, NY, 13902, United States.
Bioact Mater ; 9: 251-265, 2022 Mar.
Article in En | MEDLINE | ID: mdl-34820569
Immune checkpoint inhibitors (ICI) targeting PD-1/PD-L1 have been approved for the treatment of a variety of cancers. However, the efficacy of antibody-based ICIs could be further improved by mitigating anti-drug antibodies, proteolytic cleavage, and on-target off-tumor toxicity. One strategy for accomplishing this is through the use of extracellular vesicles (EVs), cell derived submicron vesicles with many unique properties. We constructed an engineered MDA-MB-231 cell line for harvesting EVs. This was accomplished by overexpressing a high-affinity variant human PD-1 protein (havPD-1), while simultaneously knocking out intrinsic PD-L1 and beta-2 microglobulin. The engineered havPD-1 EVs reduced PD-L1 overexpressing cancer cell proliferation and induced cellular apoptosis. Moreover, the EVs were shown to efficiently block PD-L1 mediated T cell suppression. Meanwhile antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity were not observed. The havPD-1 EVs treatment resulted in robust anti-tumor activity in both preventative co-implantation and therapeutic xenograft tumor models reconstituted with human T cells. The efficacy of the havPD-1 EVs was shown to be comparable to clinical anti-PD1 monoclonal antibodies. Additionally, loading the havPD-1 EVs with a potent PARP inhibitor was shown to further augment treatment efficacy. In brief, the engineered universal EVs harboring havPD-1 proteins can be used for cancer concurrent immunotherapy and chemotherapy.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Bioact Mater Year: 2022 Document type: Article Affiliation country: United States Country of publication: China

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Bioact Mater Year: 2022 Document type: Article Affiliation country: United States Country of publication: China