title: A comparison of the anti-tumor effects of a chimeric versus murine anti-CD19 immunotoxins on human B cell lymphoma and Pre-B acute lymphoblastic leukemia cell lines.
abstract: Precursor B cell acute lymphoblastic leukemia (pre-B ALL) affects five to six thousand adults and almost three thousand children every year. Approximately 25% of the children and 60% of the adults die from their disease, highlighting the need for new therapies that complement rather than overlap chemotherapy and bone marrow transplantation. Immunotherapy is a class of therapies where toxicities and mechanisms of action do not overlap with those of chemotherapy. Because CD19 is a B cell- restricted membrane antigen that is expressed on the majority of pre-B tumor cells, a CD19-based immunotherapy is being developed for ALL. In this study, the anti-tumor activities of immunotoxins (ITs) constructed by conjugating a murine monoclonal antibody (MAb), HD37, or its chimeric (c) construct to recombinant ricin toxin A chain (rRTA) were compared both in vitro using human pre-B ALL and Burkitt's lymphoma cell lines and in vivo using a disseminated human pre-B ALL tumor cell xenograft model. The murine and chimeric HD37 IT constructs were equally cytotoxic to pre-B ALL and Burkitt's lymphoma cells in vitro and their use in vivo resulted in equivalent increases in survival of SCID mice with human pre-B ALL tumors when compared with control mice.
authors: The Cancer Immunobiology Center, University of Texas Southwestern Medical Center at Dallas, 6000 Harry Hines Blvd, Dallas, TX 75390, USA. lydiaktsai@gmail.com
authors: Lydia K
authors: LK
authors: Tsai
authors: Laurentiu M
authors: LM
authors: Pop
authors: Xiaoyun
authors: X
authors: Liu
authors: Ellen S
authors: ES
authors: Vitetta
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D018941:Antigens, CD19 / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000276:immunology; D045744:Cell Line, Tumor; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D007167:Immunotherapy; D000922:Immunotoxins / Q000494:pharmacology*; D051379:Mice; D016513:Mice, SCID; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000276:immunology; D012276:Ricin / Q000276:immunology / Q000627:therapeutic use; D020298:U937 Cells
chemical_list: D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; D000970:Antineoplastic Agents; D000922:Immunotoxins; D012276:Ricin