Targeting CD38 and CD138 Antigens through NK Cell Immunotherapy for Effective Treatment of Multiple Myeloma

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B533
Abstract ID: 4906

Presenting Author:
Seung-Hwan Lee , Professor at Univ. Ottawa

Abstract:

Multiple myeloma (MM) is a type of cancer that develops from the uncontrollable growth of abnormal plasma cells. Due to their clonal diversity, MM cells show heterogeneous expression of tumor antigens, highlighting the importance of multi-antigen targeting for effective immunotherapies. Recently, the US Food and Drug Administration (FDA) approved Daratumumab (DARA), a CD38-targeting human monoclonal antibody, for treating MM. However, DARA also affects natural killer (NK) cells, which also express CD38, causing depletion of NK cell populations upon the DARA treatment.

To mitigate this adverse effect, the generation of CD38 knockout (KO) NK cells using CRISPR-Cas9 has emerged as a promising approach to enhance NK cell-based immunotherapy, especially when used in conjunction with DARA treatment. Additionally, targeting multiple antigens on MM cells can be achieved by combining DARA with CAR-NK cells against CD138. In our study, we created CD38 KO NK cells equipped with anti-CD138 CAR through single transduction using retroviral particles. These cells were then expanded by stimulation with feeder cells, allowing us to assess their anti-MM activity both in vitro and in vivo. Our findings, which combine DARA with CAR-NK cells, offer valuable insights into advancing effective NK cell immunotherapy for multiple myeloma.