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

https://doi.org/10.1016/j.xcrm.2020.100003Get rights and content
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Highlights

  • TFH exhibit high expression levels of PD-1

  • PD-L1 CAR-expressing NK cells selectively kill TFH but not Treg or memory T cells

  • Killing of TFH by CAR NK inhibits B cell proliferation and antibody production

  • The PD-L1 CAR represents a novel therapeutic tool in TFH-driven diseases

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.

Keywords

systemic lupus erythematosus
rheumatoid arthritis
Sjögren syndrome
allergy
cytotherapy
cytotoxicity
checkpoint
PD-L1
NK-92

Cited by (0)

13

Present address: Poseida Therapeutics, San Diego, CA 92121, USA

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Present address: Medical Scientist Training Program, The Ohio State University College of Medicine, Columbus, OH 43210, USA

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Lead Contact