title: Efficacy of a CD22-targeted antibody-saporin conjugate in a xenograft model of precursor-B cell acute lymphoblastic leukemia.
abstract: Targeted therapies, such as those using imatinib and rituximab, have revolutionized the treatment of Philadelphia chromosome-positive and CD20-positive acute lymphoblastic leukemia (ALL) respectively, yet these therapies are effective in only a subset of patients and remission is generally not durable. The next generation of targeted therapies includes the use of antibodies conjugated to potent cytotoxic agents and are classified as antibody drug conjugates (ADC). For B-lineage ALL, CD22 is an ideal target for ADC therapy because it is expressed on the majority of B-lineage ALL cells and because antibody binding mediates receptor internalization. HB22.7-SAP is a conjugate of our anti-CD22 monoclonal antibody (mAb), HB22.7, and the ribosome inhibiting protein, saporin (SAP). In vitro, HB22.7-SAP effectively bound to CD22 on the surface of pre-B ALL cell lines and exhibited potent and specific cytotoxicity. In a NOD/SCID xenograft mouse model of pre-B ALL, when compared to the vehicle-treated control, HB22.7-SAP increased the median survival time from 20 days to over 50 days without significant toxicity.
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, University of California, Davis, Cancer Center, Sacramento, CA, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Kato
authors.forename: Noriko
authors.initials: N
authors.lastname: Satake
authors.forename: Robert T
authors.initials: RT
authors.lastname: O'Donnell
authors.forename: Mastewal
authors.initials: M
authors.lastname: Abuhay
authors.forename: Carly
authors.initials: C
authors.lastname: Lewis
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Tuscano
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D054789:Ribosome Inactivating Proteins, Type 1 / Q000627:therapeutic use*; D000076985:Saporins; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000037:antagonists & inhibitors*; D014183:Transplantation, Heterologous
chemical_list: D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D054789:Ribosome Inactivating Proteins, Type 1; D051918:Sialic Acid Binding Ig-like Lectin 2; D000076985:Saporins