Immunotoxin therapy for primary malignant brain tumors

摘要: Abstract The prognosis of malignant brain tumors is poor in spite aggressive treatment. Immunotoxin therapy a novel approach for the treatment tumors. Targeted fusion toxins, chimeric protein consisting cytotoxic domain natural toxin and carrier ligands such as growth factor or an antibody, have been introduced central nervous system (CNS) tumors, with promising results. internalized into cytosol target cell via cell-surface receptors it essential these on tumor to be highly expressed order immunotoxin specific anti-tumor activity. Studies expression receptor targeting was performed transferring (TR), insulin-like factor-1 (IGF-1R), interleukin-4 (IL-4R) human glioblastoma (U373-MG T98-G) medulloblastoma (Daoy) lines, effect irradiation expressibility studied. Recombinant diphtheria toxin–murine conjugate (DT 390 –mIL4) developed its efficacy against murine (SMA-560) neuroblastoma (Neuro-2a NB41-A3) lines examined, combined tested. Receptors were all cases except IGF-1R T98-G. After irradiation, TR increased Daoy, Daoy U373-MG, IL-4R decreased U373-MG. DT –mIL4 exhibited dose-dependent, effects tested IC 50 (concentration that inhibit 50% synthesis) value 0.56×10 −9 M SMA-560, 1.28×10 Neuro-2a 0.95×10 −10 NB41-A3. Cytotoxicity additive when at 10 administered irradiation. toxins are characterized by great potency high specificity minimal damage normal neuronal tissue, one proper targets toxin. cytotoxicity administrated adjuvant modality