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Selection, Expansion, and Unique Pretreatment of Allogeneic Human Natural Killer Cells with Anti-CD38 Monoclonal Antibody for Efficient Multiple Myeloma Treatment

B. Motais, S. Charvátová, Z. Walek, M. Hrdinka, R. Smolarczyk, T. Cichoń, J. Czapla, S. Giebel, M. Šimíček, T. Jelínek, T. Ševčíková, J. Sobotka, Z. Kořístek, R. Hájek, JR. Bagó

. 2021 ; 10 (5) : . [pub] 20210421

Jazyk angličtina Země Švýcarsko

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc22004440

Grantová podpora
CZ.02.1.01/0.0/0.0/17_049/0008440 Cell Coolab Ostrava-Research and Development Center for Cell Therapy in Hematology and Oncology
CZ.02.1.01/0.0/0.0/18_069/0010060 New Directions of Biomedical Research in the Ostrava Region
IRP03_2018-2020 Institutional Development Plan of University of Ostrava, allocated by The Ministry of Education, Youth and Sports

Cellular immunotherapy is becoming a new pillar in cancer treatment after recent striking results in different clinical trials with chimeric antigen receptor T cells. However, this innovative therapy is not exempt from challenges such as off-tumor toxicity, tumor recurrence in heterogeneous tumors, and affordability. To surpass these limitations, we exploit the unique anti-tumor characteristics of natural killer (NK) cells. In this study, we aimed to obtain a clinically relevant number of allogeneic NK cells derived from peripheral blood (median of 14,050 million cells from a single donor) to target a broad spectrum of solid and liquid tumor types. To boost their anti-tumor activity, we combined allogeneic NK cells with the approved anti-cluster of differentiation 38 (CD-38) monoclonal antibody Daratumumab to obtain a synergistic therapeutic effect against incurable multiple myeloma. The combination therapy was refined with CD16 polymorphism donor selection and uncomplicated novel in vitro pretreatment to avoid undesired fratricide, increasing the in vitro therapeutic effect against the CD-38 positive multiple myeloma cell line by more than 20%. Time-lapse imaging of mice with established human multiple myeloma xenografts revealed that combination therapy of selected and pretreated NK cells with Daratumumab presented tumor volumes 43-fold smaller than control ones. Combination therapy with an allogeneic source of fully functional NK cells could be beneficial in future clinical settings to circumvent monoclonal antibodies' low therapeutic efficiency due to NK cell dysfunctionality in MM patients.

Citace poskytuje Crossref.org

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