- Experiment ID
- Experiment Name
- Experiment Type
- Transcriptomic single cell
- BCMA CAR-T is highly effective for relapsed/refractory multiple myeloma(R/R-MM) and significantly improves the survival of patients. However, the short remission time and high relapse rate of MM patients treated with BCMA CAR-T remain bottlenecks that limit long-term survival. The immune microenvironment of the bone marrow (BM) in R/R-MM may be responsible for this. The present study aims to present an in-depth analysis of resistant mechanisms and to explore potential novel therapeutic targets for relapse of BCMA CAR-T treatment via single-cell RNA sequencing (scRNA-seq) of BM plasma cells and immune cells.
- Our group launched a single-arm, single-center clinical trial on BCMA CAR-T cells in the treatment of R/R-MM on April 11, 2018. The construction of anti-BCMA CAR, lentivirus production and production of CAR-T cells were described by our previous study . Thirty-four patients with R/R-MM were treated with BCMA CAR-T cell therapy and the preliminary results have been reported in the journal of leukemia (ClinicalTrials.gov Identifier: NCT03661554) . The ORR is 88.2% and the median progression-free survival time (PFS) is 12.1 months . To analyze the mechanism of relapse after BCMA CAR-T cell therapy, one patient at baseline (R/R-MM) and one patient at progression (first relapse after BCMA CAR-T therapy) were enrolled in the study. The patient relapse after BCMA CAR-T cell therapy is from one of the 34 patients, who was enrolled in this clinical trial on December 13, 2019, and a relapse was detected on October 27, 2021(namely as progression in this study). And the other patient is from the newly enrolled, who met the criteria for enrollment in the clinical trial on December 3, 2021, after screening (namely as baseline in this study). The detailed characteristics of these two patients including clinicopathological features, bone marrow plasma cell ratio, staging and so on were comparable and similar (Additional file 1: Table S1). Five milliliters (mL) of bone marrow were then extracted from the two patients, and the CD45+ cells were enriched with human CD45 microbeads, according to the manufacturer’s instructions (Miltenyi Biotec, Cat#:130-045-801). The CD45+ cells were subsequently sent for 10 × genomics ScRNA-seq.
Identification of potential resistance mechanisms and therapeutic targets for the relapse of BCMA CAR-T therapy in relapsed/refractory multiple myeloma through single-cell sequencing
library_layout Paired mate_pair n/a insertion_size n/a number_of_reads_sequenced n/a library_name n/a library_selection cDNA_oligo_dT library_strategy RNA-Seq platform Illumina NovaSeq 6000
Project ID Project name Create Date OEP004164 Identification of potential resistance mechanisms and therapeutic targets for the relapse of BCMA CAR-T therapy in relapsed/refractory multiple myeloma through single-cell sequencing 2023-05-25
- Create Date
- Last Modified
- Jianxiang Shi
- Zhengzhou University