The safety and clinical effects of administering a multiantigen-targeted T cell therapy to patients with multiple myeloma
- 29 July 2020
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Translational Medicine
- Vol. 12 (554)
- https://doi.org/10.1126/scitranslmed.aaz3339
Abstract
Multiple myeloma (MM) is an almost always incurable malignancy of plasma cells. Despite the advent of new therapies, most patients eventually relapse or become treatment-refractory. Consequently, therapies with nonoverlapping mechanisms of action that are nontoxic and provide long-term benefit to patients with MM are greatly needed. To this end, we clinically tested an autologous multitumor-associated antigen (mTAA)–specific T cell product for the treatment of patients with high-risk, relapsed or refractory MM. In this study, we expanded polyclonal T cells from 23 patients with MM. T cells whose native T cell receptors were reactive toward five myeloma-expressed target TAAs (PRAME, SSX2, MAGEA4, Survivin, and NY-ESO-1) were enriched ex vivo. To date, we have administered escalating doses of these nonengineered mTAA-specific T cells (0.5 × 107 to 2 × 107 cells/m2) to 21 patients with MM, 9 of whom were at high risk of relapse after a median of 3 lines of prior therapy and 12 with active, relapsed or refractory disease after a median of 3.5 prior lines. The cells were well tolerated, with only two transient, grade III infusion-related adverse events. Furthermore, patients with active relapsed or refractory myeloma enjoyed a longer than expected progression-free survival and responders included three patients who achieved objective responses concomitant with detection of functional TAA-reactive T cell clonotypes derived from the infused mTAA product.Keywords
Funding Information
- National Cancer Institute (5P50CA126752)
- NIH Clinical Center (S10OD018033)
- NIH Clinical Center (S10OD023469)
- NIH Clinical Center (S10OD025240)
- American Society of Hematology (Junior Faculty Award)
- Leukemia and Lymphoma Society (SCOR)
- Edward P. Evans Foundation (Discovery Research Grant 2018)
- American Society for Blood and Marrow Transplantation (Young investigator award 2016 - 2018)
- Leukemia Texas (Research grant 2016-18)
- Leukemia and Lymphoma Society (Translational research award (rising tide foundation))
This publication has 35 references indexed in Scilit:
- Current treatment landscape for relapsed and/or refractory multiple myelomaNature Reviews Clinical Oncology, 2014
- Chimeric Antigen Receptor T Cells for Sustained Remissions in LeukemiaThe New England Journal of Medicine, 2014
- HTSeq—a Python framework to work with high-throughput sequencing dataBioinformatics, 2014
- Current Treatment for Multiple MyelomaThe New England Journal of Medicine, 2014
- Reversal of Tumor Immune Inhibition Using a Chimeric Cytokine ReceptorMolecular Therapy, 2014
- STAR: ultrafast universal RNA-seq alignerBioinformatics, 2012
- RNA-SeQC: RNA-seq metrics for quality control and process optimizationBioinformatics, 2012
- Cytotoxic T Lymphocytes Simultaneously Targeting Multiple Tumor-associated Antigens to Treat EBV Negative LymphomaMolecular Therapy, 2011
- Chimeric Antigen Receptor–Modified T Cells in Chronic Lymphoid LeukemiaThe New England Journal of Medicine, 2011
- Case Report of a Serious Adverse Event Following the Administration of T Cells Transduced With a Chimeric Antigen Receptor Recognizing ERBB2Molecular Therapy, 2010