Faculty Research 1990 - 1999

Title

Biotherapy for xenografted human central nervous system leukemia in mice with severe combined immunodeficiency using B43 (anti-CD19)-pokeweed antiviral protein immunotoxin.

Document Type

Article

Publication Date

1995

Keywords

Antibodies-Monoclonal: tu, Antigens-CD: im, Antigens-Differentiation-B-Lymphocyte: im, Blood-Brain-Barrier, Bone-Marrow: pa, Cell-Movement, Central-Nervous-System: pa, Comparative-Study, Drug-Screening, DNA-Neoplasm: an, Immunotoxins: tu, Injections-Intraperitoneal, Injections-Intravenous, Injections-Spinal, Leukemia-Lymphocytic-Acute: dt, pa, Leukemia-Pre-B-Cell: dt, pa, Leukemic-Infiltration: dt, Meninges: pa, Methotrexate: tu, Mice, Mice-SCID, Neoplasm-Circulating-Cells, Neoplasm-Transplantation, Plant-Proteins: tu, Polymerase-Chain-Reaction, Specific-Pathogen-Free-Organisms, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Transplantation-Heterologous

JAX Source

Blood 1995 May 1;85(9):2537-45

Grant

CA42633/CA/NCI, CA44114/CA/NCI, CA42111/CA/NCI

Abstract

The study of central nervous system (CNS) leukemia has been hampered by the lack of a suitable animal model. We report that severe combined immunodeficiency (SCID) mice invariably develop rapidly progressive fatal CNS leukemia within 3 weeks after intravenous injection of NALM-6 pre-B acute lymphoblastic leukemia (ALL) cells. Colonization of the dura mater and subarachnoid space, usually of the distal spinal cord with occasional extension into the Virchow-Robin spaces of blood vessels subjacent to the meninges, followed involvement of bone marrow in the skull, vertebrae, and, occasionally, the appendicular skeleton. Occult CNS leukemia was detectable by polymerase chain reaction amplification of human DNA as early as 8 days postinoculation of leukemia cells. We used this in vivo model of human CNS leukemia to examine the therapeutic efficacy and toxicity of intrathecally administered B43 (anti-CD19)-pokeweed antiviral protein (PAP), an anti-B-lineage ALL immunotoxin directed against the pan-B-cell antigen CD19/Bp95. Intrathecal therapy with B43 (anti-CD19)-PAP immunotoxin at nontoxic dose levels significantly improved survival of SCID mice and was superior to intrathecal methotrexate therapy.

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