Anti-T cell immunotoxins containing pokeweed anti-viral protein: potential purging agents for human autologous bone marrow transplantation.
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.
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D002051:Burkitt Lymphoma / Q000276:immunology / Q000628:therapy; D003602:Cytotoxicity, Immunologic; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007945:Leukemia, Lymphoid / Q000276:immunology / Q000628:therapy; D008213:Lymphocyte Activation / Q000187:drug effects; D008212:Lymphocyte Depletion; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000627:therapeutic use*; D054789:Ribosome Inactivating Proteins, Type 1; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D014021:Tissue Preservation; D014410:Tumor Stem Cell Assay
D000911:Antibodies, Monoclonal; D000972:Antineoplastic Agents, Phytogenic; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; C024275:pokeweed antiviral protein