Characterization of the anti-CD22 targeted therapy, moxetumomab pasudotox, for B-cell precursor acute lymphoblastic leukemia

Pediatr Blood Cancer. 2017 Nov;64(11):10.1002/pbc.26604. doi: 10.1002/pbc.26604. Epub 2017 Apr 27.

Abstract

Moxetumomab pasudotox is a second-generation recombinant immunotoxin against CD22 on B-cell lineages. Antileukemic activity has been demonstrated in children with chemotherapy-refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL), with variable responses. Here, we report in vitro and in vivo evaluation of moxetumomab pasudotox treatment of human cell lines and patient-derived cells as a preliminary study to understand characteristics of sensitivity to treatment. Binding, internalization, and apoptosis were evaluated using fluorescently tagged moxetumomab pasudotox. Studies in NOD-scid IL2Rgnull mice showed a modest survival benefit in mice engrafted with 697 cells but not in NALM6 or the two patient-derived xenograft models.

Keywords: acute lymphoblastic leukemia; immunotherapy.

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Bacterial Toxins / pharmacology*
  • Cell Proliferation / drug effects
  • Child
  • Child, Preschool
  • Exotoxins / pharmacology*
  • Humans
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / pathology*
  • Sialic Acid Binding Ig-like Lectin 2 / antagonists & inhibitors*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays
  • Young Adult

Substances

  • Antineoplastic Agents
  • Bacterial Toxins
  • Exotoxins
  • Sialic Acid Binding Ig-like Lectin 2
  • immunotoxin HA22