sodium-dodecyl-sulfate and Precursor-B-Cell-Lymphoblastic-Leukemia-Lymphoma

The immunotoxin BU12-SAPORIN was constructed by covalently coupling the single-chain ribosome-inactivating protein saporin to the anti-CD19 monoclonal antibody BU12 via a disulphide linker using the heterobifunctional reagent SPDP. The immunoreactivity and specificity of BU12-SAPORIN was identical to that of unmodified native BU12 antibody. BU12-SAPORIN was selectively cytotoxic in vitro in a dose-dependent manner for the CD19+ human common acute lymphoblastic leukaemia (cALL) cell line NALM-6 but exhibited no toxicity for the CD19- T-cell acute lymphoblastic leukaemia (T-ALL) cell line HSB-2. The survival of severe combined immunodeficient (SCID) mice with disseminated NALM-6 leukaemia was significantly prolonged compared with sham-treated control animals by a course of therapy with BU12-SAPORIN but not with the irrelevant anti-CD7 immunotoxin HB2-SAPORIN. BU12-SAPORIN had no therapeutic effect in SCID mice with disseminated CD19- HSB-2 leukaemia. These preclinical studies have clearly demonstrated the selective cytotoxicity of BU12-SAPORIN for CD19+ target cells both in vitro and in vivo. This, taken together with the lack of expression of the CD19 molecule by any normal life-sustaining tissue and its ubiquitous and homogeneous expression by the majority of cALL and B-NHL cells, provides the rationale for undertaking a phase I trial of systemic therapy with BU12-SAPORIN.

Topics: Animals; Antibodies, Monoclonal; Antigens, CD19; Antigens, Neoplasm; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; B-Lymphocytes; Burkitt Lymphoma; Drug Screening Assays, Antitumor; Electrophoresis, Polyacrylamide Gel; Female; Humans; Immunotoxins; Leukemia, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Mice, SCID; N-Glycosyl Hydrolases; Neoplasm Proteins; Neoplasm Transplantation; Plant Proteins; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Protein Synthesis Inhibitors; Ribosome Inactivating Proteins, Type 1; Saporins; Sodium Dodecyl Sulfate