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Primary AML and MDS blasts show high sensitivity to Debio 1562M in vitro , as well as AML LSCs (A–E) Unsorted blood cells from patients with AML ( n = 31) were assessed for (A) levels of CD37 expression and (B) levels of internalization of labeled Debio 1562M (Debio 1562M-pHRodo MFI). AML blasts were identified using CD45 and CD34 markers, B cells using CD19, and T cells using CD3. (C) The same AML samples were cultured in the presence of increasing doses of Debio 1562M and the viability of the malignant blasts assessed. (D) AML patient samples classified by mutational or pre-treatment status versus sensitivity to Debio 1562M (IC50). (E) Viability of AML blasts and normal B and T cells at 100 nM dose of Debio 1562M are shown. (F) Relative colony-forming units of primary AML samples ( n = 13) following incubation with vehicle, an isotype antibody ADC, or Debio 1562M (1 or 10 nM) for 48 h. (G–J) Unsorted blood cells from patients with MDS ( n = 15) were assessed for (G) levels of CD37 expression and (H) levels of internalization of labeled Debio 1562M (Debio 1562M-pHRodo MFI). MDS blasts were identified using CD34, CD33, and <t>HLA-DR</t> markers; B cells using CD19; and T cells using CD3. (I) The MDS samples analyzed above were cultured in the presence of increasing doses of Debio 1562M and the viability of the malignant blasts assessed. (J) Viability of MDS blasts and normal B and T cells at 100 nM dose of Debio 1562M are shown. Shown are mean ± SEM. One-way ANOVA multiple comparison was used for statistical analysis ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001. See also and and and .
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Primary AML and MDS blasts show high sensitivity to Debio 1562M in vitro , as well as AML LSCs (A–E) Unsorted blood cells from patients with AML ( n = 31) were assessed for (A) levels of CD37 expression and (B) levels of internalization of labeled Debio 1562M (Debio 1562M-pHRodo MFI). AML blasts were identified using CD45 and CD34 markers, B cells using CD19, and T cells using CD3. (C) The same AML samples were cultured in the presence of increasing doses of Debio 1562M and the viability of the malignant blasts assessed. (D) AML patient samples classified by mutational or pre-treatment status versus sensitivity to Debio 1562M (IC50). (E) Viability of AML blasts and normal B and T cells at 100 nM dose of Debio 1562M are shown. (F) Relative colony-forming units of primary AML samples ( n = 13) following incubation with vehicle, an isotype antibody ADC, or Debio 1562M (1 or 10 nM) for 48 h. (G–J) Unsorted blood cells from patients with MDS ( n = 15) were assessed for (G) levels of CD37 expression and (H) levels of internalization of labeled Debio 1562M (Debio 1562M-pHRodo MFI). MDS blasts were identified using CD34, CD33, and HLA-DR markers; B cells using CD19; and T cells using CD3. (I) The MDS samples analyzed above were cultured in the presence of increasing doses of Debio 1562M and the viability of the malignant blasts assessed. (J) Viability of MDS blasts and normal B and T cells at 100 nM dose of Debio 1562M are shown. Shown are mean ± SEM. One-way ANOVA multiple comparison was used for statistical analysis ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001. See also and and and .

Journal: Cell Reports Medicine

Article Title: Debio 1562M CD37-targeting ADC is highly active and well tolerated in preclinical models of AML and MDS

doi: 10.1016/j.xcrm.2026.102749

Figure Lengend Snippet: Primary AML and MDS blasts show high sensitivity to Debio 1562M in vitro , as well as AML LSCs (A–E) Unsorted blood cells from patients with AML ( n = 31) were assessed for (A) levels of CD37 expression and (B) levels of internalization of labeled Debio 1562M (Debio 1562M-pHRodo MFI). AML blasts were identified using CD45 and CD34 markers, B cells using CD19, and T cells using CD3. (C) The same AML samples were cultured in the presence of increasing doses of Debio 1562M and the viability of the malignant blasts assessed. (D) AML patient samples classified by mutational or pre-treatment status versus sensitivity to Debio 1562M (IC50). (E) Viability of AML blasts and normal B and T cells at 100 nM dose of Debio 1562M are shown. (F) Relative colony-forming units of primary AML samples ( n = 13) following incubation with vehicle, an isotype antibody ADC, or Debio 1562M (1 or 10 nM) for 48 h. (G–J) Unsorted blood cells from patients with MDS ( n = 15) were assessed for (G) levels of CD37 expression and (H) levels of internalization of labeled Debio 1562M (Debio 1562M-pHRodo MFI). MDS blasts were identified using CD34, CD33, and HLA-DR markers; B cells using CD19; and T cells using CD3. (I) The MDS samples analyzed above were cultured in the presence of increasing doses of Debio 1562M and the viability of the malignant blasts assessed. (J) Viability of MDS blasts and normal B and T cells at 100 nM dose of Debio 1562M are shown. Shown are mean ± SEM. One-way ANOVA multiple comparison was used for statistical analysis ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001. See also and and and .

Article Snippet: Combinations of the following antibodies were used for flow cytometry: naratuximab [20nM; Debiopharm], CD19-PE-Cy7 [0.5μg/ml; Beckman Coulter], CD33-APC [0.9 μg/mL Biolegend], CD3-APC-H7 [1.5 μg/mL; BD Biosciences], CD19-APC-Cy7 [1.255 μg/mL; Biolegend], CD33-BV450 [1 μg/mL; BD Biosciences], HLA-DR-PE [25 μg/mL Immunostep], CD45-BV510 [2.5 μg/mL; Fisher Scientific], CD64-BV605 [3.5 μg/mL; Biolegend], CD34-PE-Cy7 [1.5 μg/mL; Biolegend], CD123-APC [1.5 μg/mL; Biolegend], CD3-AF700 [3.5 μg/mL; Biolegend].

Techniques: In Vitro, Expressing, Labeling, Cell Culture, Incubation, Comparison