Journal: bioRxiv

Article Title: Defining the RNA Modification Landscape of Multiple Myeloma Reveals METTL3-Dependent m 6 A Regulation of NEAT1

doi: 10.64898/2026.04.04.716518

Figure Lengend Snippet: a. Venn diagram showing overlap of m 6 A-modified lncRNAs identified by direct RNA-seq and meRIP-Seq. b. Read depth of NEAT1 m 6 A sites identified by direct RNA-seq. c. NEAT1 m 6 A site positions identified by both direct RNA-seq (red) and meRIP-Seq (blue). d-f. meRIP RT-qPCR data validating m 6 A site 1611 on NEAT1 in d. RPMI 8226, e. MM.1S, and f. MM.1R relative to negative control IgG. ILF3 mRNA serves as positive control and GAPDH serves as negative control. *fold enrichment > 5, # fold enrichment > 50, n.s. not significant.

Article Snippet: MM.1R cell lines were purchased from ATCC (catalog number CRL-2975) and authenticated.

Techniques: Modification, RNA Sequencing, Quantitative RT-PCR, Negative Control, Positive Control

Journal: bioRxiv

Article Title: Defining the RNA Modification Landscape of Multiple Myeloma Reveals METTL3-Dependent m 6 A Regulation of NEAT1

doi: 10.64898/2026.04.04.716518

Figure Lengend Snippet: a. UMAP plot of B and plasma single-cell RNA sequencing data for METTL3 (left plot) from healthy (red) and multiple myeloma (MM) patients (blue) (right plot). b. Expression of METTL3 in MM samples compared to healthy samples. c and d . Expression of METTL3 and NEAT1 following small interfering RNA (siRNA)-mediated METTL3 knockdown in c. MM.1S cells and d. RPMI 8226 cells. e. Decreased viability in MM.1S cells following siRNA-mediated METTL3 knockdown, as measured by ApoTox-Glo assay. f. Decreased viability and increased apoptosis in RPMI 8226 cells following siRNA-mediated METTL3 knockdown, as measured by ApoTox-Glo assay. g. Expression of METTL3 and NEAT1 in MM.1R cells with a METTL3 overexpression vector. h. Increased viability and decreased apoptosis in MM.1R cells with a METTL3 overexpression vector, as measured by ApoTox-Glo assay. i. m 6 A blot showing global m 6 A levels in MM cells after 72-hour treatment with METTL3 inhibitor STM2457. j. Decreased viability and increased apoptosis in RPMI 8226 cells with increasing concentrations of STM2457 treatment, as measured by ApoTox-Glo assay k. Decreased viability in RPMI 8226 cells with increasing concentrations of STM2457 treatment, as measured by Celltiter-Glo Assay. *p value < 0.05, **p value < 0.005, ***p value < 0.0005, #p value < 0.00005, n.s. not significant

Article Snippet: MM.1R cell lines were purchased from ATCC (catalog number CRL-2975) and authenticated.

Techniques: Clinical Proteomics, Single Cell, RNA Sequencing, Expressing, Small Interfering RNA, Knockdown, Glo Assay, Over Expression, Plasmid Preparation

Journal: Cell Reports Medicine

Article Title: Targeting BCMA in multiple myeloma with a trifunctional NK cell engager

doi: 10.1016/j.xcrm.2026.102628

Figure Lengend Snippet: SAR’514 outperforms FcγRIIIa-engager in vitro and mediates dose-dependent anti-MM activity in vivo (A) Comparison of cytotoxicity of BCMA-NKp46-FcγRIIIa NKCE (CODV-1:1-ADE; red) and FcγRIIIa-based NK cell engager molecule targeting BCMA (FcγRIIIa-engager-tool; blue). RPMI 8226 and MM.1R cells were used as targets, with purified resting NK cells as effectors. Data from two representative NK donors out of n = 10 (RPMI 8226) and n = 6 (MM.1R) are shown. (B) EC 50 and maximum cytotoxicity activity of BCMA-NKp46-FcγRIIIa NKCE (CODV-1:1-ADE; red) and FcγRIIIa-engager (blue) against RPMI 8226 and MM.1R cells. Delta maximum lysis (Δ Max lysis) and EC 50s were determined from dose-response curves and plotted for each HMCL-NK donor pair ( n = 10 for RPMI 8226, n = 6 for MM.1R). Paired t test, two-tailed; ∗∗ p ≤ 0.01, ∗ p ≤ 0.05. (C) (Upper) Experimental setup. Human NK cells were purified and amplified in vitro for 14 days in the presence of K562 cells engineered to express CD86 and 4-1BB ligand, IL-15 (50 U/mL), and IL-21 (100 U/mL). Expanded NK cells were adoptively transferred into irradiated NOG-IL-15-Tg mice ( n = 10 per group) 7 days before MM1.R HMCL engraftment (day 0). Mice were treated once on day 1 with BCMA-NKp46-FcγRIIIa NKCE at doses of 0.05, 0.5, 2.5, 5, and 10 mg/kg, or with the IC-NKp46-FcγRIIIa NKCE control molecule at 5 mg/kg. (Lower) Kaplan-Meier survival curves of treated mice. Endpoint significance was calculated in a log rank (Mantle-Cox) test. n = 10/group. ∗ p < 0.05, ∗∗∗∗ p < 0.0001. See also and .

Article Snippet: NCI-H929 (ATCC CRL-9068), MM.1S (ATCC CRL-2974), MM.1R (ATCC CRL-2975) and RPMI 8226 (ATCC CCL-155) human myeloma cell lines (HMCLs), and HUT78 cutaneous T cell lymphoma cell line (ATCC TIB-161), were purchased at American Type Culture Collection (ATCC, USA).

Techniques: In Vitro, Activity Assay, In Vivo, Comparison, Purification, Lysis, Two Tailed Test, Amplification, Irradiation, Control

Journal: bioRxiv

Article Title: Reprogramming BCMA-Targeted CAR-T Cells through γ-Secretase Modulation Blocks Antigen Shedding and Extends CAR-T Longevity

doi: 10.64898/2026.01.20.700575

Figure Lengend Snippet: (A) Structural modeling of murine 4C8A clone versus LLM-based humanized scFv variants showing preserved CDR orientation toward BCMA and specificity for the distinct epitope. (B) RMSD plots for the snapshots from MD simulation of the scFvs (murine and humanized) in complex with BCMA TM with three technical replicates. (C) MM/GBSA based free energy binding plots for the murine and humanized scFv-BCMA complexes. (D) Workflow of immunogenicity assay showing antibody-primed dendritic cells co-cultured with autologous PBMCs. (E-G) Cytokine analysis of IFN-γ, IL-2, and IL-4 showing lower levels for humanized CARs versus murine. Fully human IgG antibody was used as reference control. (H) Representative super-resolution imaging shows uniform membrane localization of CAR constructs (magenta). Nuclei were stained with DAPI (blue). Corresponding bar graph of the image analysis (n=6). (I1) Dot plots of flow cytometry quantification of CAR surface expression using GS-linker antibody (I2) Bar graph of the flow cytometry data showing percentage CAR-Transduction (n=5). (J1) Cell-based binding assay using flow cytometry showing affinity gain for the CDR-optimized humanized CAR (HmzCAR) (J2) Bar graph of the analysis (n=5). (K) Workflow of BLI sensorgrams and kinetic analysis. (L1, L2) Bio-layer interferometry (BLI) sensogram showing real-time binding kinetics of the indicated analytes. Colored traces represent different concentrations, with an initial association phase followed by dissociation. (M) Experimental workflow of co-culture of CAR-T cells with BCMA expressing target cells. (N) Cytotoxicity against MM.1S cells across different E:T ratios (O) Similarly, for MM.1R cells (n=5). (P) Representative flow cytometry contour plots of granzyme-B secretion (P2) Mean fluorescence intensity (MFI) of the flow cytometry contour plots. Data represent mean ± SEM. *p < 0.05; **p < 0.01; ***p < 0.005; ****p < 0.001. A non-parametric t-test was used for statistical analysis between groups.

Article Snippet: The cell lines MM.1R, HEK293T, HS-5, K562, HeLa, HepG2, A549, SH-SY5Y, Raji, NALM-6, and Jurkat were obtained from ATCC, while MM.1S was purchased from BPS Biosciences.

Techniques: Binding Assay, Immunopeptidomics, Cell Culture, Control, Imaging, Membrane, Construct, Staining, Flow Cytometry, Expressing, Transduction, Cell Binding Assay, Co-Culture Assay, Fluorescence