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: NK cell engager/CODV-2:2-DE , Sanofi , In this paper.

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

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: BCMA-NKp46-FcγRIIIa NKCE promotes NK cell activation and MM cell killing ex vivo (A) Cytotoxicity of MM patient-derived PBMCs ( n = 13 ) against Karpas 620 MM cells (100:1 PBMC-to-target ratio). Cells were treated with dose range of BCMA-NKp46-FcγRIIIa NKCE (0.0005–80 nM, white circles) or IC-NKp46-FcγRIIIa NKCE (80 nM, black squares). (B) Karpas 620 cell death and MM patient NK cell activation in response to BCMA-NKp46-FcγRIIIa NKCE treatment (80 nM). Resting PBMCs from MM patients were co-cultured with Karpas 620 cells and treated with BCMA-NKp46-FcγRIIIa NKCE, IC-NKp46-FcγRIIIa NKCE, daratumumab, or obinutuzumab (all at 80 nM). NK cell activation was assessed by flow cytometry, measuring CD107a expression and intracellular production of IFN-γ and MIP-1β. Karpas 620 cell death was determined via flow cytometry based on CD38 and CD138 staining modulation. Data for all MM patients ( n = 13) are shown, with individual patient values corresponding to same symbols as in (A). One-way ANOVA Tukey’s multiple comparison test; ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001. Mean (horizontal bar) and error (SD) are indicated on graphs. See also and .

Article Snippet: NK cell engager/CODV-2:2-DE , Sanofi , In this paper.

Techniques: Activation Assay, Ex Vivo, Derivative Assay, Cell Culture, Flow Cytometry, Expressing, Staining, Comparison

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 promotes autologous NK cell activation and MM cell killing ex vivo (A) NK cell activation and myeloma cell killing in BM samples from 13 MM patients at the time of diagnosis ( n = 3) or relapse/progression ( n = 10). BM mononuclear cells were treated with SAR’514 (80 nM) and analyzed by flow cytometry after 18 h. Untreated samples served as controls. (Left) Percent myeloma cell death. (Right) Percent CD69-positive cells among CD3 − CD56 + NK cells. (Paired t test, two-tailed; ∗∗ p < 0.01, ∗∗∗ p < 0.0005). (B and C) NK cell activity against autologous MM cells of PCL patients ( n = 3). PBMCs from patients with PCL were treated with SAR’514 (80 nM, black histogram), daratumumab (140 nM, gray histogram), or isotype control NKCE (80 nM, white histogram), and death of MM cells was assessed by flow cytometry after 18 h. Myeloma cells were identified as CD3 − CD138 + cells. (B) CD138 and CD3 staining of PBMCs and gating on CD3 − CD138 + myeloma cells. Percentages of MM cell population among PBMCs are indicated on graphs in (C). Presence of myeloma cells in samples treated with SAR’514 or daratumumab, expressed as percent relative to control condition (IC-NKp46-FcγRIIIa NKCE). (D) Correlation between SAR’514-mediated myeloma cell killing and effector-to-target (NK:MM) ratio in all patient samples ( n = 14). The NK:MM ratio was calculated based on absolute counts of CD138 + myeloma cells and NK cells (CD3 − CD56 + ) by flow cytometry. Spearman r correlation, p < 0.0001, r = 0.9149. Patients with cytogenetic hallmarks associated with high risk ( samples with 17p deletion , del17p , and/or 1q gain , 1q , and/or t(4 ; 14) translocation) are indicated by a star. See also .

Article Snippet: NK cell engager/CODV-2:2-DE , Sanofi , In this paper.

Techniques: Activation Assay, Ex Vivo, Biomarker Discovery, Flow Cytometry, Two Tailed Test, Activity Assay, Control, Staining, Translocation Assay