PRE-CLINICAL DEVELOPMENT OF BB-NK-001: AN ACADEMIC MEMORY-LIKE NK CELL THERAPY FOR THE TREATMENT OF ACUTE MYELOID LEUKEMIA — ASN Events
  1. Schedule
  2. Poster Session Two
  3. PRE-CLINICAL DEVELOPMENT OF BB-NK-001: AN ACADEMIC MEMORY-LIKE NK CELL THERAPY FOR THE TREATMENT OF ACUTE MYELOID LEUKEMIA

PRE-CLINICAL DEVELOPMENT OF BB-NK-001: AN ACADEMIC MEMORY-LIKE NK CELL THERAPY FOR THE TREATMENT OF ACUTE MYELOID LEUKEMIA (#225)

Victor V Sanda 1 2 , Itxaso I Gartzia-Aranaga 2 , Susana S Calvo-Martinez 2 , Alba A Luzuriaga-Alvarez 2 , Ana Maria AM Perez-Lopez 2 , Miren Sorne MS Solaun-Aguirre 3 , Maria Dolores MD García-Vázquez 3 , Victoria V Mielgo 4 , Carmen C Rey-Santano 4 , Itxaso I San Juan 1 , Ainhoa A Amarilla-Irusta 1 , Ainara A Lopez-Pardo 1 , Gabirel G Astarloa-Pando 1 , Ferran F Borràs-Grañana 1 , Olatz O Zenarruzabeitia 1 5 , Laura L Amo 1 6 , Juan Jose JJ Mateos-Mazon 7 8 , Javier J Arzuaga-Mendez 7 8 , Beatriz B Martin-Antonio 9 , Rosario R Sanchez-Pernaute 2 6 , Elena E Amutio 7 8 , Juan Carlos JC Garcia-Ruiz 7 8 , Francisco F Borrego 1 6
  1. Immunopathology Group, Biobizkaia Health Research Institute (HRI), Barakaldo, Basque Country, Spain
  2. Advanced Therapies Production Unit, Biobizkaia Health Research Institute (HRI), Barakaldo, Basque Country, Spain
  3. Flow cytometry and cell culture facilities, Biobizkaia HRI, Barakaldo, Basque Country, Spain
  4. Animal facility, Biobizkaia HRI, Barakaldo, Basque Country, Spain
  5. Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), Leioa, Basque Country, Spain
  6. Ikerbasque, Basque Foundation for Science, Bilbao, Basque Country, Spain
  7. Department of Hematology, Cruces University Hospital, Barakaldo, Basque Country, Spain
  8. Hematological Cancer Group, Biobizkaia HRI, Barakaldo, Basque Country, Spain
  9. Department for the Development of Advanced Therapy Medicinal Products, Instituto de Salud Carlos III, Madrid, Spain

Background: Cytokine-induced memory-like (CIML) natural killer (NK) cells are generated through the preactivation of NK cells with interleukins (IL)-12/15/18, and exhibit improved anti-tumor activity, making them a promising option for treating acute myeloid leukemia (AML) and other cancers. Automated cell processing systems like the CliniMACS Prodigy® (Miltenyi Biotec) facilitate the cost-effective production of Good Manufacturing Practices (GMP)-compliant cell therapies in academic settings.

Aims: To produce an academic CIML NK cell product, named BB-NK-001, using the CliniMACS Prodigy® system, to characterize the produced cells and to evaluate their efficacy.

Methods: BB-NK-001 cells were produced in the CliniMACS Prodigy® from leukapheresis from healthy donors as follows. NK cells were isolated (CD3+ cell depletion followed by CD56+ cell selection) and preactivated for 16-18h with IL-12/15/18. After incubation, the cells were harvested and freshly used. They were phenotypically characterized by flow cytometry. Their effector functions and cytotoxic activity were evaluated against hematological cancer cell lines (K562, 721.221, Jurkat, Ramos) and primary AML blasts, and their proliferation in response to IL-2 was also measured. Non-preactivated NK cells were also used as controls. Preactivated NK cell biodistribution was also assessed in immunodeficient NSG mice.

Results: BB-NK-001 cells were successfully produced, and highly enriched in NK cells with an increased expression of the activation-induced markers CD25, CD69, and CD137 compared to control NK cells. Additionally, BB-NK-001 showed greater proliferation ability in response to IL-2, a higher degranulation (CD107a expression), higher production of effector cytokines (IFN-γ and TNF-α), and an increased cytotoxic activity against tumor cells than control NK cells. The in vivo biodistribution of preactivated NK cells was observed in blood, spleen, bone marrow, lungs, and liver of NSG mice.

Conclusion: BB-NK-001 cells were successfully produced and shown to be effective against hematological tumors, including AML, highlighting their potential as a cancer therapy.