Journal
CLINICAL CANCER RESEARCH
Volume 15, Issue 3, Pages 951-959Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-08-1823
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Funding
- National Cancer Institute [R01 CA913569, R01 CA103978]
- Leukemia and Lymphoma Society Translational Research Grants
- Multiple Myeloma Research Foundation
- Commonwealth Foundation for Cancer Research
- International Myeloma Foundation
- Lymphoma Research Foundation
- American Society of Hematology
- University Cancer Foundation
- Center for Targeted Therapy of The University of Texas M. D. Anderson Cancer Center
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Purpose: We showed recently that anti-beta(2)-microglobulin (beta M-2) monoclonal antibodies (mAb) have remarkably strong apoptotic effects on myeloma cells in vitro and in SCID-hu mice. However, whether the mAbs will be therapeutic and safe in the treatment of myeloma patients, in whom every tissue expresses low densities of MHC class I molecules and elevated levels of soluble beta M-2 are present, remains to be determined. Experimental Design: In this study, human-like myeloma mouse models (HLA-A2-transgenic NOD/SCID mice) were developed, which express mature and functional human MHC class I (HLA-A2 and human beta M-2) on murine organs and present high levels of circulating human beta M-2 derived from human myeloma cells. Myeloma-bearing mice were treated intraperitoneally with anti-beta M-2 mAbs, and the distribution and effects of the mAbs on normal organs and established tumors were examined. Results: Our results show that anti-beta M-2 mAbs were effective in suppressing myeloma growth in treated mice. The therapeutic efficacy of the mAbs in these mice are comparable with those observed in myeloma-bearing nontransgenic NOD/SCID mice in which no human MHC class I is expressed on murine organs. Furthermore, although the mAbs can be detected on different organs, no tissue damage or cell apoptosis was observed in the mice. Conclusion: Based on the antimyeloma efficacy and low toxicity in the mice, our study suggests that anti-beta M-2 mAbs may be safe and the tissue-expressing and soluble beta M-2 may not compromise their therapeutic effects in myeloma patients. This study provides further support for the future application of the mAbs as therapeutic agents for multiple myeloma.
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