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Targeted therapy for HM1.24 (CD317) on multiple myeloma cells
1Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medical Sciences, 3-18-15 Kuramoto, Tokushima 770-8503, Japan.
Abstract:
Multiple myeloma (MM) still remains an incurable disease, at least because of the existence of cell-adhesion mediated drug-resistant MM cells and/or continuous recruitment of presumed MM cancer stem cell-like cells (CSCs). As a new alternative treatment modality, immunological approaches using monoclonal antibodies (mAbs) and/or cytotoxic T lymphocytes (CTLs) are now attracting much attention as a novel strategy attacking MM cells. We have identified that HM1.24 [also known as bone marrow stromal cell antigen 2 (BST2) or CD317] is overexpressed on not only mature MM cells but also MM CSCs. We then have developed a humanized mAb to HM1.24 and defucosylated version of the mAb to adapt to clinical practice. Moreover, we have successfully induced HM1.24-specific CTLs against MM cells. The combination of these innovative therapeutic modalities may likely exert an anti-MM activity by evading the drug resistance mechanism and eliminating presumed CSCs in MM.
Insights
Multiple myeloma (MM) remains incurable due to drug-resistant cells and cancer stem cells (CSCs). Researchers developed a novel immunotherapy targeting HM1.24, a protein found on both mature MM cells and CSCs, offering a potential new treatment strategy.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Multiple myeloma (MM) is an incurable blood cancer.
- Drug-resistant MM cells and cancer stem cells (CSCs) contribute to treatment failure.
- Immunological approaches, including monoclonal antibodies (mAbs) and cytotoxic T lymphocytes (CTLs), show promise for MM treatment.
Purpose of the Study:
- To investigate HM1.24 (BST2/CD317) as a therapeutic target in MM.
- To develop novel immunotherapeutic strategies against MM, including targeting MM CSCs.
- To evaluate the potential of combining HM1.24-targeted mAbs and CTLs for MM treatment.
Main Methods:
- Identified HM1.24 overexpression on mature MM cells and MM CSCs.
- Developed a humanized mAb against HM1.24, including a defucosylated version for clinical use.
- Generated HM1.24-specific CTLs for potential anti-MM immunotherapy.
Main Results:
- HM1.24 is confirmed to be overexpressed on both mature MM cells and MM CSCs.
- Successfully developed a humanized anti-HM1.24 mAb and induced HM1.24-specific CTLs.
- The developed immunotherapeutic agents show potential for clinical application against MM.
Conclusions:
- HM1.24 is a promising therapeutic target for multiple myeloma.
- Combination immunotherapy targeting HM1.24 may overcome drug resistance and eliminate MM CSCs.
- This novel approach offers a potential strategy to improve outcomes for patients with multiple myeloma.
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