ORIGINAL RESEARCH article
Front. Immunol.
Sec. NK and Innate Lymphoid Cell Biology
Automated manufacturing of clinical-grade BDCA2 CAR NK cells in a closed system for the treatment of blastic plasmacytoid dendritic cell neoplasm
Provisionally accepted
Rita Pfeifer1Sabine Müller1Marcus Nitsche1Melanie Sohmen1
Julia Kostyra1Arthur Bister1Cathrin Bleilevens1Janina Brauner1Angela Mekes1Juliane Raasch1Dominika Lukas1Jens Kopatz1Wael Al Rawashdeh1Marsilius Mues1José Alberto Villacorta Hidalgo1
Volker Huppert1Mario Assenmacher1Nina Möker1
Rimas Orentas2
Congcong Zhang1*- 1Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany
- 2Lentigen Technology, Inc., a Miltenyi Biotec Company, Gaithersburg, MD, United States
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Recent progress in chimeric antigen receptor (CAR) natural killer (NK) cell therapy has demonstrated their promising potential in cancer immunotherapy. However, most current CAR NK cell manufacturing processes utilize open systems with multiple manual steps, making it challenging to maintain consistent therapeutic quality and regulatory compliance for clinical applications. We specifically developed blood dendritic cell antigen 2 (BDCA2)-targeting CAR NK cells for treating blastic plasmacytoid dendritic cell neoplasm (BPDCN). Here, we present an automated, current good manufacturing practice (cGMP)-compliant Natural Killer Cell Transduction (NKCT) process for producing clinical-grade CAR NK cells on the CliniMACS Prodigy® platform. This closed system integrates cell separation, activation, transduction, expansion, and harvest, thereby reducing contamination risks and ensuring cell product quality. The NKCT process achieved high transduction efficiency using baboon envelope pseudotyped lentiviral vectors (BaEV-LV) produced under cGMP conditions combined with Vectofusin®-1, yielding CAR NK cells with high viability and purity. Both in vitro and in vivo studies demonstrated the potent antitumor activity of CliniMACS Prodigy-manufactured BDCA2 CAR NK cells, highlighting a promising treatment strategy for BPDCN. In summary, this automated NKCT process enables both centralized and decentralized CAR NK manufacturing and facilitates the efficient clinical translation of CAR NK cell therapies.
Keywords: Automated manufacturing, BDCA2 CAR, BPDCN, cancer immunotherapy, CAR NK cells, CliniMACSProdigy NKCT
Received: 05 Dec 2025; Accepted: 13 Feb 2026.
Copyright: © 2026 Pfeifer, Müller, Nitsche, Sohmen, Kostyra, Bister, Bleilevens, Brauner, Mekes, Raasch, Lukas, Kopatz, Al Rawashdeh, Mues, Villacorta Hidalgo, Huppert, Assenmacher, Möker, Orentas and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Congcong Zhang
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