We are investigating a new approach for the treatment of brain tumors which utilizes a new delivery approach for distribution of a class of potent, targeted anti-cancer compounds, called targeted protein toxins. Preclinical in vitro and in vivo experiments of toxins targeted to the transferrin receptor and epidermal growth factor (EGF) demonstrated significant antitumor activity against a variety of tumor types, including malignant gliomas. New methods of drug delivery have been developed to deliver these agents to brain tumors, and in vivo imaging methods are being developed to demonstrate drug distribution in patients. We have completed a phase I trial of regional therapy with the targeted protein toxin transferrin-CRM 107 (Tf-CRM107) for the treatment of recurrent malignant brain tumors. Tf-CRM107 is a conjugate of human transferrin (Tf) and diphtheria toxin with a point mutation (CRM107). Tf-CRM107 binds to the Tf receptor, which facilitates iron uptake and is present in higher number on tumor cells than on the normal cells of the brain; the diphtheria toxin mutant kills tumor cells to which the Tf-CRM107 binds. The purpose of the Phase I study was to evaluate the toxicity of Tf-CRM107 when delivered by intratumoral and peritumoral slow interstitial infusion in a dose escalation schedule and to assess antitumor activity in these patients. Twenty-seven patients with malignant brain tumors refractory to standard therapy (surgery, radiation chemotherapy) were treated. The results indicated that therapy with Tf-CRM107 produces tumor responses without severe neurologic or systemic toxicity. A multicenter Phase II study has now begun. Synergism between targeted protein toxins and other antitumor agents, including standard chemotherapy drugs and retinoids, is under investigation.
| Park, Deric M; Zhuang, Zhengping; Chen, Ling et al. (2007) von Hippel-Lindau disease-associated hemangioblastomas are derived from embryologic multipotent cells. PLoS Med 4:e60 |
| Szerlip, Nicholas J; Fox, Elizabeth; Manosca, Frances et al. (2007) Pancreatoblastoma metastases to the brain. Case illustration. J Neurosurg 106:169 |
| Butman, John A; Kim, H Jeffrey; Baggenstos, Martin et al. (2007) Mechanisms of morbid hearing loss associated with tumors of the endolymphatic sac in von Hippel-Lindau disease. JAMA 298:41-8 |
| Mehta, Gautam U; Shively, Sharon B; Glasker, Sven et al. (2007) von Hippel-Lindau disease: epididymal cystadenoma targeted by metastatic events. Urology 69:1209.e9-12 |
| Glasker, Sven; Lonser, Russell R; Okamoto, Hiroaki et al. (2007) Proteomic profiling: a novel method for differential diagnosis? Cancer Biol Ther 6:343-5 |
| Baggenstos, Martin A; Butman, John A; Oldfield, Edward H et al. (2007) Role of edema in peritumoral cyst formation. Neurosurg Focus 22:E9 |
| Jaikumar, Sivakumar; Zhuang, Zhengping; Mannan, Poonam et al. (2007) Interspecies comparative genomic hybridization (I-CGH): a new twist to study animal tumor models. Cell Cycle 6:836-42 |
| Jagannathan, Jay; Butman, John A; Lonser, Russell R et al. (2007) Endolymphatic sac tumor demonstrated by intralabyrinthine hemorrhage. Case report. J Neurosurg 107:421-5 |
| Weil, Robert J; Vortmeyer, Alexander O; Nieman, Lynnette K et al. (2006) Surgical remission of pituitary adenomas confined to the neurohypophysis in Cushing's disease. J Clin Endocrinol Metab 91:2656-64 |
| Oldfield, Edward H; Vortmeyer, Alexander O (2006) Development of a histological pseudocapsule and its use as a surgical capsule in the excision of pituitary tumors. J Neurosurg 104:7-19 |
Showing the most recent 10 out of 63 publications
