Journal: Molecular Therapy Oncology
Article Title: A measles virus encoding a CD19/CD3 bispecific T cell engager shows enhanced preclinical anti-BCP-ALL efficacy without significant toxicity
doi: 10.1016/j.omton.2026.201127
Figure Lengend Snippet: MV-Blina therapy significantly prolongs the survival of ALL bearing mice (A) Treatment scheme. Two PDX models were established in NSG mice by i.v. injection to induce ALL. At a leukemic load of approximately 35%, mice received treatment i.v. with MV (2.5 × 10 5 TCID 50 /g) or control. Two days after infection, mice were injected with healthy human PBMCs. (B) Superior survival of PDX #2 with MV-Blina compared to MV-Edm. PDX #1 and #2 were treated either with MV-Blina and PBMC ( n = 10) or MV-Edm and PBMC ( n = 10) or control with PBMC only ( n = 10) and observed for a maximum of 70 days. (C) MV-Blina treatment decreases leukemic load. Leukemic blasts (msCD45 − huCD19 + huCD45 dim ) and human PBMC (msCD45 − huCD19 + huCD45 bright ) in peripheral blood were monitored by flow cytometry at the indicated time points. (D) Marked reduction of spleen weight in PDX upon MV-Blina treatment. At the time of death, a complete necropsy was performed, and spleen weight was determined. (E) Significant reduction of leukemic blasts by MV-Blina in ALL compartments. At the time of death, leukemic blasts (msCD45 − huCD19 + huCD45 dim ) were detected by flow cytometry in bone marrow, spleen, and meninges. Replication of secBlina was detected by qRT-PCR and calculated by the 2 −ΔΔCt method, displaying the fold change relative to huActin and huGAPDH. (F) MV-Blina reduces leukemic blasts in the spleen by decreasing proliferation and increasing apoptosis. Spleens of untreated mice at therapy start (d0, n = 4) and treated mice (MV-Blina and PBMC, n = 10; MV-Edm and PBMC, n = 9; PBMC-only control, n = 9) were formalin-fixed, paraffin-embedded, and subsequently stained for H&E, CD22, Ki67, or cleaved Caspase-3 (CC3). Positive area was determined using ImageJ. Scale bars 50 μm. Statistical analysis was performed using Mantel-Cox log rank test (B), one-way ANOVA with Tukey’s multiple comparisons test (C-F). ns, not significant; ∗, p < 0.05; ∗∗, p < 0.01; ∗∗∗, p < 0.001; and ∗∗∗∗, p < 0.0001.
Article Snippet: Immunohistochemistry for CD22 was performed using a mouse anti-human CD22 antibody (clone OTI1F2, 1:75, TA506404, Origene, Rockville, MD), for Ki67 using a mouse anti-human Ki67 antibody (clone MIB-1, 1:150, M7240, Dako, Waldbronn, Germany) and for cleaved caspase-3 (CC3) using a rabbit-anti human active caspase-3 antibody (1:200, ab13847, Abcam, Cambridge, UK).
Techniques: Injection, Control, Infection, Flow Cytometry, Quantitative RT-PCR, Formalin-fixed Paraffin-Embedded, Staining