Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors
We investigated regional therapy of recurrent malignant brain tumors with transferrin-CRM107, a conjugate of human transferrin (Tf) and a genetic mutant of diphtheria toxin (CRM107) that lacks native toxin binding. Physiological barriers to delivering proteins to tumor and surrounding infiltrated br...
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| Veröffentlicht in: | Nature medicine 1997-12, Vol.3 (12), p.1362-1368 |
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| creator | Laske, Douglas W Youle, Richard J Oldfield, Edward H |
| description | We investigated regional therapy of recurrent malignant brain tumors with transferrin-CRM107, a conjugate of human transferrin (Tf) and a genetic mutant of diphtheria toxin (CRM107) that lacks native toxin binding. Physiological barriers to delivering proteins to tumor and surrounding infiltrated brain were circumvented with high-flow interstitial microinfusion. At least a 50% reduction in tumor volume on magnetic resonance imaging (MRI) occurred in 9 of 15 patients who could be evaluated (60%), including two complete responses. Peritumoral toxicity developed 1–4 weeks after treatment in three of three patients at 1.0 μg/ml, but in zero of nine patients treated at lower concentrations. No symptomatic systemic toxicity occurred. Regional perfusion with Tf-CRM107 produces tumor responses without systemic toxicity in patients with malignant brain tumors refractory to conventional therapy. Direct interstitial infusion can be used successfully to distribute a large protein in the tumor and infiltrated brain surrounding the tumor. |
| doi_str_mv | 10.1038/nm1297-1362 |
| format | Article |
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Physiological barriers to delivering proteins to tumor and surrounding infiltrated brain were circumvented with high-flow interstitial microinfusion. At least a 50% reduction in tumor volume on magnetic resonance imaging (MRI) occurred in 9 of 15 patients who could be evaluated (60%), including two complete responses. Peritumoral toxicity developed 1–4 weeks after treatment in three of three patients at 1.0 μg/ml, but in zero of nine patients treated at lower concentrations. No symptomatic systemic toxicity occurred. Regional perfusion with Tf-CRM107 produces tumor responses without systemic toxicity in patients with malignant brain tumors refractory to conventional therapy. 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| subjects | Adult Aged Antibodies - blood Biomedical and Life Sciences Biomedicine Brain - metabolism Brain - pathology Brain Neoplasms - pathology Brain Neoplasms - therapy Cancer Research Diphtheria Toxin - adverse effects Diphtheria Toxin - genetics Diphtheria Toxin - therapeutic use Drug Design Female Humans Infectious Diseases Magnetic Resonance Imaging Male Metabolic Diseases Middle Aged Molecular Medicine Neurosciences Transferrin - adverse effects Transferrin - genetics Transferrin - therapeutic use |
| title | Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors |
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