Blockade of Integrin-?4- Mediated Adhesion of T-ALL Cells - Abstract
Objective: We showed previously that ?4 blockade using a humanized monoclonal antibody against integrin ?4, Natalizumab, antagonizes stromal adhesion of pre-B ALL cells and in combination with chemotherapy eliminates resistant pre-B-ALL in an MRD setting. Here we determined the effect of Natalizumab on adherence of patientderived T-ALL cells in vitro and on survival prolongation of murine recipients of T-ALL cells, to explore the potential of Natalizumab as a novel T-ALL treatment strategy.
Methods: Adhesion to stromal matrix proteins in the presence/absence of Natalizumab and survival of murine recipients of primary T-ALL cells treated with/without Natalizumab were assessed, using previously described methods.
Results: Natalizumab inhibited adhesion of patient-derived T-ALL cells and attenuated leukemia progression, resulting in prolonged survival of recipient NOD/SCID IL2R gamma-/- mice of patient-derived T-ALL.
Conclusion: ?4 blockade interferes with adhesion of T-ALL cells to its counter receptor and thus merits evaluation as a novel adjuvant strategy for T-ALL. Further study is needed to explore at the molecular level the effect of ?4 blockade in T-ALL.