hubcma expressing el4 cells  (ATCC)

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: 1:1 BCMA-NKp46-FcγRIIIa NKCE drives anti-tumor activity in vitro and in vivo (A) Schematic of BCMA-NKp46-FcγRIIIa NKCE mode of action. The molecule binds to BCMA on MM cells and recruits/activates NK cells by co-engaging NKp46 and FcγRIIIa, leading to MM cell killing and/or cytokine production. (B) (Left) Cytotoxicity comparison of F25, CODV-1:1, CODV-2:1, BCMA-IgG1, and IC-NKp46-FcγRIIIa NKCE control (IC-F25). RPMI 8226 and MM.1S MM cells were used as targets, with purified resting NK cells from 4 healthy donors as effectors. (Right) EC 50 and maximum cytotoxic activity of BCMA-IgG1 and BCMA-NKp46-FcγRIIIa NKCE against RPMI 8226 and MM.1S MM cells. Delta maximum lysis (ΔMax lysis)—defined as percent maximum lysis minus background lysis of the isotype control (IC-F25) at corresponding concentration—and EC 50s were monitored from dose-response curves after 4-h incubation, plotted separately for all MM cell lines and NK donors ( n = 4). ANOVA/Tukey’s multiple comparisons test ∗ p < 0.05, ∗∗∗ p < 0.0005. (C) Comparison of cytotoxicity between 1:1 (F25, CODV-1:1) and 2:2 (F33, CODV-2:2) BCMA-NKp46-FcγRIIIa NKCE formats with the same setting as in (B). Two representative NK donors are shown ( n = 17). (D) (Left) Flow cytometry analysis of fluorescent RMA cells expressing human BCMA ( dsRed ) or lacking BCMA expression ( eGFP ), showing BCMA expression only on dsRed cells. (Middle) Experimental setup. A 2:3 mixture of eGFP (BCMA-negative) and dsRed (BCMA-positive) RMA cells was intravenously injected into huNKp46-Tg x Rag1 −/− transgenic mice. Tumor-bearing mice ( n = 27–28 per group) received a single dose of 12.5 pmol/animal (0.078 mg/kg) of BCMA-NKp46-FcγRIIIa NKCEs or vehicle control. Liver biopsies were collected 48 h post-treatment, and infiltrating RMA cells quantified by flow cytometry. (Right) Flow cytometry analysis of BCMA expression on dsRed RMA cells pre-engraftment ( in vitro , red histogram) and post-engraftment in liver biopsies (gray histogram). (E) (Left) Absolute count of liver-infiltrated RMA cells. (Right) dsRed/eGFP cell ratio in liver biopsies, analyzed by flow cytometry 48 h after treatment. Statistical analysis: Mann-Whitney test (ns, p > 0.05; ∗ p < 0.01). (F) Kaplan-Meier survival curves for huNKp46-Tg x Rag1−/− mice bearing disseminated EL4-huBCMA tumors treated with BCMA-NKp46-FcγRIIIa NKCEs lacking Fc optimization for enhanced ADCC. Treatment groups (red) received 5, 0.5, or 0.05 mg/kg of BCMA-NKp46-FcγRIIIa NKCE, compared to the isotype control NKCE (gray, 5 mg/kg) and vehicle (black). Statistical analysis: log rank (Mantel-Cox) test ( p < 0.05, ∗ p = 0.0398, ∗∗ p = 0.0082, ∗∗∗ p = 0.0001, ∗∗∗∗ p < 0.0001). See also .

Article Snippet: huBCMA-expressing EL4 cells (wild type EL4 cell line obtained from ATCC, TIB-39) , Sanofi , This paper.

Techniques: Activity Assay, In Vitro, In Vivo, Comparison, Control, Purification, Lysis, Concentration Assay, Incubation, Flow Cytometry, Expressing, Injection, Transgenic Assay, MANN-WHITNEY

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: ADCC-optimized BCMA-NKp46-FcγRIIIa NKCE drives anti-tumor activity in vitro and in vivo (A) Comparison of cytotoxicity of BCMA-NKp46-FcγRIIIa NKCE molecules engineered for enhanced ADCC (-ADE) vs. non-engineered (wild-type Fc) counterparts. RPMI 8226 MM cells were used as target, and purified resting NK cells served as effector. Data from one representative NK cell donor is shown ( n = 13). (B) EC 50 and maximum cytotoxic activity of F25 ( N = 21), F25-ADE ( N = 13), CODV-1:1 ( N = 29), CODV-1:1-ADE ( n = 14), F33 ( n = 15), F33-ADE ( n = 13), CODV-2:2 ( n = 23), and CODV-2:2-ADE ( n = 13) molecules against RPMI 8226 MM cells. ΔMax lysis and EC 50s were determined from dose-response curves and plotted separately for each NK donor. Statistical analysis: ANOVA/Tukey’s multiple comparisons test (∗ p < 0.005; ∗∗∗ p < 0.0001). (C) Kaplan-Meier survival curves for huFcγR-Tg mice bearing disseminated EL4-huBCMA tumors and treated with surrogate BCMA-moNKp46-FcγRIIIa NKCE lacking ADCC optimization (wild-type Fc) ( CODV-1 : 1 , pink) or ADCC-optimized BCMA-moNKp46-FcγRIIIa NKCE ( CODV-1 : 1-ADE , blue) at 0.5 mg/kg. Statistical analysis: log rank (Mantel-Cox) test (∗∗ p < 0.001). See also and .

Article Snippet: huBCMA-expressing EL4 cells (wild type EL4 cell line obtained from ATCC, TIB-39) , Sanofi , This paper.

Techniques: Activity Assay, In Vitro, In Vivo, Comparison, Purification, Lysis