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CD38-CAR Natural Killer Cells: Potential Immunotherapy Target in Multiple Myeloma?

By: Joseph Fanelli
Posted: Monday, October 24, 2022

Findings presented at the 2022 International Myeloma Society (IMS) Annual Meeting and Exposition (Abstract P-010) suggest that CD38–chimeric antigen receptor (CAR) natural killer (NK) cells may be strong immunotherapy candidates for future patients with multiple myeloma. Evren Alici, MD, PhD, of the Karolinska Institutet, Stockholm, and colleagues found that autologous NK cells offer a feasible and safe therapeutic option.

In this study, the investigators used a retroviral approach to introduce a high-affinity CD38-targeting CAR construct to CD38-low cytokine-expanded peripheral blood NK cells from healthy donors. The authors demonstrated a reproducible transgene expression from 40% to 60% and assessed the functionality of the CAR NK cells in in vitro assays.

The investigators discovered that CD38-CAR NK cells yielded a threefold increase in degranulation and a twofold higher specific target cell lysis of CD38-positive multiple myeloma cell lines when compared with unmodified NK cells. In addition, the specific cytotoxicity of the CD38-CAR NK cells was confirmed against CD38-negative multiple myeloma target cell lines generated with the CRISPR/Cas9 technology.

After translating their approach to expanded peripheral blood NK cells for three patients newly diagnosed with multiple myeloma—who later were refractory to anti-CD38 antibody treatment—the authors revealed a 5% to 25% transduction efficacy, with increased cytotoxic potential for CAR-expressing NK cells against autologous bone marrow samples that were CD138-positive.

Disclosure: Study authors’ disclosure information not provided.

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