2. Academic Validation
  3. Synthetic libraries of immune cells displaying a diverse repertoire of chimaeric antigen receptors as a potent cancer immunotherapy

Synthetic libraries of immune cells displaying a diverse repertoire of chimaeric antigen receptors as a potent cancer immunotherapy

  • Nat Biomed Eng. 2022 Jul;6(7):842-854. doi: 10.1038/s41551-022-00895-1.
Wenyan Fu  # 1,  Changhai Lei  # 2 3,  Chuqi Wang 2 3,  Zetong Ma 2 3,  Tian Li 2 3,  Fangxing Lin 2 3,  Ruixue Mao 3,  Jian Zhao 4,  Shi Hu 5 6
Affiliations

Affiliations

  • 1 Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 Department of Biophysics, College of Basic Medical Sciences, Naval Medical University (Second Military Medical University), Shanghai, China.
  • 3 Team NMU-China of the International Genetically Engineered Machine Competition, Department of Biophysics, Naval Medical University (Second Military Medical University), Shanghai, China.
  • 4 KOCHKOR Biotech, Inc., Shanghai, China.
  • 5 Department of Biophysics, College of Basic Medical Sciences, Naval Medical University (Second Military Medical University), Shanghai, China. hus@smmu.edu.cn.
  • 6 Team NMU-China of the International Genetically Engineered Machine Competition, Department of Biophysics, Naval Medical University (Second Military Medical University), Shanghai, China. hus@smmu.edu.cn.
  • # Contributed equally.
PMID: 35668107 DOI: 10.1038/s41551-022-00895-1
Abstract

Cancer immunotherapies rely on one or few specific tumour-associated antigens. However, the adaptive immune system relies on a large and diverse repertoire of Antibodies for antigen recognition. Here we report the development and applicability of libraries of immune cells displaying diverse repertoires of chimaeric antigen receptors (CARs) that can recognize non-self antigens and display antigen-dependent clonal expansion, with the expanded population of tumour-specific effector cells leading to long-lasting antitumour responses in mouse models of epithelial tumours. The intravenous injection of synthetic libraries of murine CARs on TET2- T cells led to robust immunological memory and the recognition of mutated or evolved tumours, owing to the maintenance of CAR diversity. Off-the-shelf libraries of 106 murine or human CAR clones displayed on genetically modified human NK-92 Cancer cells completely eliminated established tumours in mice with murine xenografts and patient-derived xenografts. Synthetically generated CAR libraries may aid the discovery of new CARs and the development of immunotherapies.

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