Bispecific killer engager for targeted depletion of PD-1 positive lymphocytes: A new avenue for autoimmune disease treatment

https://doi.org/10.1016/j.apsb.2024.10.014

This new article publication from Acta Pharmaceutica Sinica B, discusses a bispecific killer engager for targeted depletion of PD-1 positive lymphocytes.

Bispecific killer cell engagers (BiKEs) are a powerful tool to incite the killing power of natural killer (NK) cells. The authors of this article posit that the BiKE technology could be utilized to deplete activated immune cells expressing programmed death-1 (PD-1⁺ cells), and hence treat autoimmune diseases since these cells drive the disorders. They designed and generated PD-1 BiKE that targets an activating NK cell receptor, CD16, and PD-1. PD-1 BiKE showed specific binding to PD-1⁺ cells and engaged CD16 simultaneously. PD-1 BiKE enhanced NK cell-mediated apoptosis and depletion of PD-1⁺ Raji cells, but not PD-1^- Raji cells. Further, PD-1 BiKE induced apoptosis of primary PD-1⁺ T lymphocytes that are highly relevant to autoimmune disease progression. The BiKE depleted 42% of primary T cells that were stimulated in vitro. Importantly, those ablated primary T cells were activated cells. Meanwhile, naive T cells were spared by the BiKE treatment, supporting the crucial selectivity of PD-1 BiKE-directed cell depletion. Lastly, PD-1 BiKE is more effective than a conventional depleting antibody in the depletion of PD-1⁺ cells. The current work supports PD-1 BiKE is a selective, potent, and safe tool to deplete PD-1⁺ cells.

Keywords: Immunotherapy; Bispecific killer engager; Bispecific antibody; PD-1-positive cells; Autoimmune disease; Natural killer cell; PD-1; Antibody-dependent cellular cytotoxicity

Graphical Abstract: available at https://ars.els-cdn.com/content/image/1-s2.0-S2211383524004155-ga1_lrg.jpg

PD-1 BiKE that targets an activating NK cell receptor, CD16, and PD-1 was designed and generated, which supports PD-1 BiKE is a selective, potent, and safe tool to deplete PD-1⁺ cells.

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The Journal of the Institute of Materia Medica, the Chinese Academy of Medical Sciences and the Chinese Pharmaceutical Association.

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CiteScore: 22.4

Impact Factor: 14.8 (Top 5 journal in the category of Pharmacology and pharmacy)

JIF without self-citation: 13.9

ISSN 2211-3835

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Lauren C. Naatz, Shuyun Dong, Brian Evavold, Xiangyang Ye, Mingnan Chen, Bispecific killer engager for targeted depletion of PD-1 positive lymphocytes: A new avenue for autoimmune disease treatment, Acta Pharmaceutica Sinica B, Volume 15, Issue 3, 2025, Pages 1230-1241, ISSN 2211-3835, https://doi.org/10.1016/j.apsb.2024.10.014.