Targeting CD138-/CD20+ Clonogenic Myeloma Precursor Cells Decreases These Cells and Induces Transferable Antimyeloma Immunity
| Autor: | Elyse N. Tomaszewski, Lawrence G. Lum, Lois Ayash, Hiroshi Yano, Muneer H. Abidi, Sri Vidya Kondadasula, Dana Schalk, Voravit Ratanatharathorn, Archana Thakur, Joseph P. Uberti, Abhinav Deol, Zaid Al-Kadhimi, Jeffrey A. Zonder |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Adult Male Article 03 medical and health sciences 0302 clinical medicine Autologous stem-cell transplantation Immunity immune system diseases hemic and lymphatic diseases Antibodies Bispecific Medicine Humans Clonogenic assay Autografts Multiple myeloma Pretargeting Aged CD20 Transplantation biology business.industry Hematology Middle Aged medicine.disease Antigens CD20 Immunity Humoral 030104 developmental biology medicine.anatomical_structure surgical procedures operative 030220 oncology & carcinogenesis Immunology biology.protein Neoplastic Stem Cells Female Bone marrow Syndecan-1 Antibody business Multiple Myeloma human activities Stem Cell Transplantation |
| Zdroj: | Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 22(5) |
| ISSN: | 1523-6536 |
| Popis: | This phase Ib clinical trial evaluated whether pretargeting of CD20+ clonogenic myeloma precursor cells (CMPCs) with anti-CD3 × anti-CD20 bispecific antibody-armed T cells (BATs) before autologous stem cell transplantation (SCT) in patients with standard-risk and high-risk multiple myeloma would induce antimyeloma immunity that could be detected and boosted after SCT. All 12 patients enrolled in this study received 2 BATs infusions before SCT, and 4 patients received a booster infusion of BATs after SCT. Pretargeting CD138−/CD20+ CMPCs with BATs before SCT was safe and reduced levels of CMPCs by up to 58% in the postinfusion bone marrow in patients who remained in remission. Four of 5 patients who remained in remission had a >5-fold increase in IFN-γ enzyme-linked immunospot responses. SOX2 antibody increased after BATs infusions and persisted after SCT. The median anti-SOX2 level at 3 months after SCT was 28.1 ng/mL (range, 4.6 to 256 ng/mL) in patients who relapsed and 46 ng/mL (range, 28.3 to 73.3 ng/mL) in patients who remained in remission. The immune correlates suggest that infusions of targeted T cells given before SCT were able to reduce CMPC levels and induced cellular and humoral antimyeloma immunity that could be transferred and boosted after SCT. |
| Databáze: | OpenAIRE |
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