Selective depletion of PD-1 positive lymphocytes using a novel bispecific killer engager

Selective depletion of PD-1 positive lymphocytes using a novel bispecific killer engager

This new article publication byActa Pharmaceutica Sinica Bdiscusses a bispecific killer engager for the targeted depletion of PD-1-positive lymphocytes.

Bispecific killer cell engagers (Bikes) are a powerful tool to increase the killing power of natural killer (NK) cells. The authors of this article bet that cycling technology could be used to deplete activated immune cells that express programmed death undertaking-1 (PD-1+ cells) and therefore treat autoimmune diseases as these cells drive the disorders. They designed and created PD-1 bike, which targets an activating NK cell receptor, CD16 and PD-1. The PD-1 bike showed specific binding to PD-1+ cells and delivered CD16 simultaneously. PD-1 cycling increased NK cell-mediated apoptosis and degradation of PD-1+ Raji cells but not PD-1-Raji cells.

Furthermore, PD-1 cycling induced the apoptosis of primary PD-1+ T lymphocytes, which are of great importance for the progression of autoimmune diseases. The bike depleted 42% of the primary T cells that were stimulatedin vitro. Importantly, these ablated primary T cells were activated cells. Meanwhile, naïve T cells were spared by cycling treatment, supporting the crucial selectivity of PD-1 cycling-directed cell depletion. Lastly, PD-1 bicycle is more effective than a traditional depletion antibody in depleting PD-1+ cells. The current work supports that PD-1 cycling is a selective, effective and safe tool to deplete PD-1+ cells.

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