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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.
AuthorsLydia K Tsai, Laurentiu M Pop, Xiaoyun Liu, Ellen S Vitetta
JournalToxins (Toxins (Basel)) Vol. 3 Issue 4 Pg. 409-19 (04 2011) ISSN: 2072-6651 [Electronic] Switzerland
PMID22069716 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Antigens, CD19
  • Antineoplastic Agents
  • Immunotoxins
  • Ricin
Topics
  • Animals
  • Antibodies, Monoclonal (immunology, therapeutic use)
  • Antigens, CD19 (immunology)
  • Antineoplastic Agents (pharmacology)
  • B-Lymphocytes (drug effects, immunology)
  • Burkitt Lymphoma (drug therapy, immunology)
  • Cell Line, Tumor
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Humans
  • Immunotherapy
  • Immunotoxins (pharmacology)
  • Mice
  • Mice, SCID
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, immunology)
  • Ricin (immunology, therapeutic use)
  • U937 Cells

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