Zhang, M., Loh, H. P., Goh Fang, S., Yang, Y., Lam, K.-P., & Xu, S. (2024). Development of BCMA-Targeted Bispecific Natural Killer Cell Engagers for Multiple Myeloma Treatment. Antibodies, 13(4), 97. https://doi.org/10.3390/antib13040097
Abstract:
Background: B-cell maturation antigen (BCMA)-targeted T cell-redirecting immunotherapies, including Chimeric Antigen Receptor (CAR) T-cell therapy and T-cell engagers have demonstrated remarkable success in treating relapsed/refractory (RR) multiple myeloma (MM), a malignancy of plasma cells. However, a significant challenge is the severe side effects associated with T-cell overactivation, leading to cytokine release syndrome and neurotoxicity in MM patients undergoing such therapies. Bispecific NK cell engagers (NKCEs) may offer a promising alternative by redirecting NK cell cytotoxic activity towards tumor cells without triggering cytokine release syndrome. Methods: In this study, we designed a series of BCMA × CD16 NKCEs that simultaneously engage BCMA and CD16 on MM and NK cells, respectively. We evaluated the functionality of these NKCEs in vitro with respect to their molecular design. Results: Our results indicate that the format design of NKCEs influences their functionalities, underscoring the importance of format selection in optimizing NKCE-based therapies for MM. This study provides valuable insights for developing next-generation NKCEs and advancing therapeutic strategies for MM and potentially other malignancies.
License type:
Attribution 4.0 International (CC BY 4.0)
Funding Info:
This research / project is supported by the National Research Foundation - Competitive Research Programme
Grant Reference no. : CRP26-2021RS-0002
This research is supported by core funding from: Agency for Science, Technology and Research
Grant Reference no. :