Therapeutic Targeting of Follicular T Cells with Chimeric Antigen Receptor-Expressing Natural Killer Cells

Cell Reports Medicine

Arthur T. de la Cruz-Lynch¹  Leah C. Kottyan²  Kelly M. Rangel²  Marat V. Khodoun³  Stacey A. Cranert³  Hermine I. Brunner⁴  Ivayla E. Gyurova⁵  Jasmine A. Tuazon⁵  David F. Smith⁵  Ayad Ali⁵  Stephen N. Waggoner⁵  Seth D. Reighard⁵ 

[1] Division of Developmental Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA;Immunology Graduate Training Program, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA;Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA;Pathobiology and Molecular Medicine Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA;Center for Autoimmune Genomics and Etiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA;

关键词: systemic lupus erythematosus;    rheumatoid arthritis;    Sjögren syndrome;    allergy;    cytotherapy;    cytotoxicity;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Follicular helper T cells (TFH) are critical for vaccine and infection elicitation of long-lived humoral immunity, but exaggerated TFH responses can promote autoimmunity and other pathologies. It is unfortunate that no clinical interventions exist for the selective depletion of follicular T cells to alleviate these diseases. We engineered a chimeric antigen receptor (CAR) facilitating the specific targeting of cells with high expression levels of human programmed cell death protein 1 (PD-1), a cardinal feature of follicular T cells. CAR-expressing human natural killer (NK) cells robustly and discriminately eliminated PD-1high follicular human T cells in vitro and in a humanized mouse model of lupus-like disease while sparing B cells and other PD-1low T cell subsets, including regulatory T cells. These results establish a strategy for specific targeting of PD-1high T cells that can be advanced as a clinical tool for the selective depletion of pathogenic follicular T cells or other PD-1high target cells in certain disease states.

【 授权许可】

Unknown