1. Targeting CD138−/CD20+ Clonogenic Myeloma Precursor Cells Decreases These Cells and Induces Transferable Antimyeloma Immunity.
- Author
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Lum, Lawrence G., Thakur, Archana, Kondadasula, Sri Vidya, Al-Kadhimi, Zaid, Deol, Abhinav, Tomaszewski, Elyse N., Yano, Hiroshi, Schalk, Dana L., Ayash, Lois, Zonder, Jeffrey A., Uberti, Joseph P., Abidi, Muneer H., and Ratanatharathorn, Voravit
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CD antigens , *MULTIPLE myeloma treatment , *CANCER cell analysis , *CELLULAR immunity , *ANTINEOPLASTIC agents , *CLINICAL trials - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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