| Autor: |
Giuliana Decorti, Gabriele Stocco, Marco Rabusin, Alberto Tommasini, Elisa Piscianz, Marilena Granzotto, Raffaella Franca, Stefania Braidotti |
| Přispěvatelé: |
Braidotti, S., Franca, R., Granzotto, M., Piscianz, E., Tommasini, A., Rabusin, M., Stocco, G., Decorti, G. |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| DOI: |
10.31083/j.fbl2702039 |
| Popis: |
Background: The T-cell engager antibody blinatumomab (BlincytoTM) represents a promising rescue therapy for relapsed/refractory CD19+ acute lymphoblastic leukemia (B-ALL), although ∼20-30% of patients still do not respond to treatment. Blinatumomab creates a tight synapsis between CD3+ T-lymphocytes and leukemic CD19+ B-cells, resulting in a granzyme B (GzB)-mediated specific lysis of leukemic cells. Methods: Aim of the study was to provide evidence that variability in blinatumomab response could have a genetic basis in PAX5, one of the most often mutated genes in B-ALL, affecting the CD19 surface expression on lymphoblasts, and could be explored in vitro by means of a cytofluorimetric assay, staining both surface antigens (CD45, CD19 and CD3) and intracytoplasmic markers (7AAD, Syto16). Two human immortalized B-ALL cell lines (NALM6 and REH) were chosen for their different PAX5 and CD19 protein levels, as verified by western blot and flow cytometry, respectively. Results: In contrast to NALM6, REH cells do not express the full-length PAX5 protein and show less CD19 on the cell surface (fluorescence peak median intensity: 9155 versus 28895). Co-cultures of CD3+ T-lymphocytes from healthy donors and B-ALL cell lines were seeded at an effector-to-target cell ratio of 1:10 for simulating the condition existing in the bone marrow due to the malignant invasion of blast cells. Co-cultures were exposed in vitro to blinatumomab and the simultaneous increase in blast mortality and T-lymphocytes activation induced by the drug was observed at day +7 (both effects: P |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
