Anti-T cell immunotoxins containing pokeweed anti-viral protein: potential purging agents for human autologous bone marrow transplantation
Autor: | Ramakrishnan S, Fatih M. Uckun, Ll, Houston |
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Předmět: |
Cytotoxicity
Immunologic Time Factors T-Lymphocytes Antibodies Monoclonal Bone Marrow Cells Hematopoietic Stem Cells Lymphocyte Activation Antineoplastic Agents Phytogenic Burkitt Lymphoma Lymphocyte Depletion Leukemia Lymphoid Bone Marrow Ribosome Inactivating Proteins Type 1 Humans Tissue Preservation N-Glycosyl Hydrolases Tumor Stem Cell Assay Bone Marrow Transplantation Plant Proteins |
Zdroj: | Europe PubMed Central |
Popis: | The ex vivo anti-leukemic efficacy and stem cell toxicity of two different T cell directed immunotoxins containing pokeweed antiviral protein (PAP) were studied by clonal assays. 5E9-11-PAP, an immunotoxin directed against human transferrin receptors, elicited a maximum leukemic cell kill of 3.9 logs. However, it was also toxic against normal pluripotent stem cells, and therefore is not a clinically useful purgative reagent. PAP conjugated to 3-A1, a monoclonal antibody directed against CD7 (T, p41), was more effective against leukemic T cells than 5E9-11-PAP and eliminated a maximum of 4.8 log of cells. 3A1-PAP was only slightly toxic to pluripotent stem cells: 13% of CFU-GEMM were lost after treatment with 3000 ng of 3A1-PAP/ml, a concentration that eliminated 99.96% of contaminating leukemic T cells from a 200-fold excess of normal bone marrow. Cryopreservation of treated cells by conventional methods did not affect the extreme selectivity and potency of 3A1-PAP. Incubation of 3A1-PAP with peripheral blood mononuclear cells resulted in the complete inhibition of phytohemagglutinin-induced mitogenic response, illustrating the possibility of using this immunotoxin as a potent anti-T cell reagent for prophylaxis against graft vs host disease in allogeneic BMT as well. |
Databáze: | OpenAIRE |
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