Moxetumomab pasudotox

Moxetumomab pasudotox (CAT 8015) is anti-CD22 immunotoxin containing an anti-CD22 Fv and Pseudomonas exotoxin. CD22 is a cell surface receptor expressed on a variety of malignant B-cells. Moxetumomab pasudotox can be used in the research of hairy cell leukemia (HCL)[1][2][3].

Research Areas >> Cancer

Signaling Pathways >> Others >> Others

Moxetumomab pasudotox (0-10 mg/mL, 66 h) reduces cell viability of BCP-ALL cells (determined by Annexin-V negative)[3]. The binding and internalization of MP/CD22 complexes is correlated with pre-B ALL cell line responses to MP[5].

Moxetumomab pasudotox (300 mg/kg, i.v., every other day) prolongs median survival in 697 cell model (P < 0.0001)[3]. Moxetumomab pasudotox (0.4 mg/kg, i.v. three doses, every other day) clears the bone marrow (BM) from acute lymphoblastic leukemia (ALL), but disease relapses from discrete BM-sites in NSG mouse model[4]. Animal Model: NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) mouse model[4] Dosage: 0.4 mg/kg Administration: Intravenous injection (i.v.), three doses, every other day. Result: Survived much longer but died from ALL after 40 d. Reduced BM-infiltration to 4% on day 8.

[1]. Kreitman RJ, et al. Moxetumomab pasudotox in heavily pre-treated patients with relapsed/refractory hairy cell leukemia (HCL): long-term follow-up from the pivotal trial. J Hematol Oncol. 2021 Feb 24;14(1):35.  

[2]. hillon S. Moxetumomab Pasudotox: First Global Approval. Drugs. 2018 Nov;78(16):1763-1767.  

[3]. Kinjyo I, et al. 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.  

[4]. Müller F, et al. 5-Azacytidine prevents relapse and produces long-term complete remissions in leukemia xenografts treated with Moxetumomab pasudotox. Proc Natl Acad Sci U S A. 2018 Feb 20;115(8):E1867-E1875.  

[5]. Ksenia Matlawska-Wasowska, et al. Variability In Precursor B ALL Killing With Moxetumomab Pasudotox (CAT-8015) Linked To Differential Binding and Endocytic Trafficking. Blood (2013) 122 (21): 5022.