Cincinnati Children’s hospital laboratory led a study that discovered a possible treatment for autoimmune diseases using T cells and CAR NK-cells.
Adaptive or acquired immunity is a specific response to pathogens. An important aspect of adaptive immunity and memory is the T-cell help to B cells. The support to B cells is provided by follicular helper CD4 T cells and entails helping B cells to produce antibodies against invading pathogens. Although follicular helper T cells are needed for long-term immunity, exaggerated responses of these T cells can lead to adverse reactions, including the promotion of autoimmune reactions.
A way to address diseases resulting from excessive responses of follicular helper T cells is to target and decrease this cell population. To this end, research has been conducted to target a specific feature of the helper T cells, expressed programmed cell death protein 1 (PD-1). Researchers created chimeric antigen receptor (CAR) natural killer (NK) cells that target and destroy PD-1 expressing follicular T cells in vitro and in mouse models of a disease similar to lupus in humans. The CAR NK cells can target and destroy PD-1−expressing T cells without affecting other T cell types.
The experimental CAR NK cells caused cytolytic degranulation on PD-1−expressing cells in vitro, such as human follicular T helper and tumor cells. The in vitro reduction of the T cells led to a decrease in memory B cell proliferation and differentiation, as well as a reduction of immunoglobulin secretion. In the lupus mouse models, high PD-1−expressing CD4 T cells and splenomegaly were reduced.
The study results suggest that the use of CAR NK cells may be an essential clinical approach to addressing autoimmune and other disease conditions associated with an excessive immune response to pathogens. Other clinically useful features of CAR NK cells are the better safety profile when compared to CAR T cells and the lower costs associated with their production and subsequent potential “off-the-shelf availability.” The clinical application of CAR NK cells may represent a viable approach to depleting high PD-1−expressing T cells responsible for immune-based diseases.
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Reighard, S., Cranert, S., Rangel, K., Ali, A., Gyurova, I., & de la Cruz-Lynch, A. et al. (2020). Therapeutic Targeting of Follicular T Cells with Chimeric Antigen Receptor-Expressing Natural Killer Cells. Cell Reports Medicine, 1(1), 100003. doi: 10.1016/j.xcrm.2020.100003
Novel CAR NK-cell technology could lead to new treatments for lupus, other incurable diseases. (2020). Retrieved 16 June 2020, from https://finance.yahoo.com/news/novel-car-nk-cell-technology-130000784.html