We are proposing a fundamentally new approach for the treatment of malignant brain tumors. The discovery and development, by members of this NCDDC, of biodegradable and biocompatible controlled release polymers has enabled us to bypass the limitations of the blood-brain barrier and expose the growing brain tumor to high drug concentrations for extended intervals. This approach can effectively administer chemotherapeutic agents as well as rationally designed new drugs and biological agents. The local, prolonged release of drugs at the site of tumor growth exposes the tumor to high levels of the drug while minimizing systemic exposure and toxicity and therefore health care costs. Program l, headed by Dr Henry Brem, will investigate the effectiveness and safety of new formulations of controlled-release drug delivery for the treatment of brain tumors. Program 2, headed by Dr. Robert Langer, will provide new polymer formulations. Program 3, headed by Dr. W. Mark Saltzman, will construct mathematical models for predicting drug distribution and clearance in the brain. Program 4, headed by Dr. O. Michael Colvin, will develop chemotherapy agents which are appropriate for incorporation into polymers for local therapy and design new agents. Program 5, headed by Dr. Drew Pardoll, will investigate polymer delivery of cytokines to develop brain tumor vaccines. Core B, headed by Dr. Craig Smith, will provide polymers that are prepared with new methods and develop the scale up and purification of the polymers. The programs of this NCDDG have been working together as a cohesive, collaborative group. Our productivity is reflected in a number of new discoveries by this group which hassled to over 150 publications during the past four years, most of which involve interactions between the different programs. This cooperative effort has allowed us to design and carry out a series of pre-clinical studies to evaluate this new, potentially curative, cancer treatment. Our effort has led to the initiation of five multi-institutional, FDA-approved clinical trials of BCNU impregnated polymers. The NCI is funding a separate UO1 for a Hopkins Clinical Consortium to support Phase 1 testing of the polymers developed in this NCDDG. We are hopeful that with the continued support and participation of the NCI we can continue to interact synergistically and develop fully the promise of this new approach.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program--Cooperative Agreements (U19)
Project #
3U19CA052857-10S3
Application #
6344314
Study Section
Special Emphasis Panel (SRC (08))
Project Start
1990-06-15
Project End
2000-09-30
Budget Start
1999-07-26
Budget End
2000-09-30
Support Year
10
Fiscal Year
2000
Total Cost
$69,151
Indirect Cost
Name
Johns Hopkins University
Department
Neurology
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Gabikian, Patrik; Tyler, Betty M; Zhang, Irma et al. (2014) Radiosensitization of malignant gliomas following intracranial delivery of paclitaxel biodegradable polymer microspheres. J Neurosurg 120:1078-85
Tyler, Betty; Wadsworth, Scott; Recinos, Violette et al. (2011) Local delivery of rapamycin: a toxicity and efficacy study in an experimental malignant glioma model in rats. Neuro Oncol 13:700-9
Slager, Joram; Tyler, Betty; Shikanov, Ariella et al. (2009) Local controlled delivery of anti-neoplastic RNAse to the brain. Pharm Res 26:1838-46
Pradilla, Gustavo; Wang, Paul P; Gabikian, Patrik et al. (2006) Local intracerebral administration of Paclitaxel with the paclimer delivery system: toxicity study in a canine model. J Neurooncol 76:131-8
Sampath, Prakash; Rhines, Laurence D; DiMeco, Francesco et al. (2006) Interstitial docetaxel (taxotere), carmustine and combined interstitial therapy: a novel treatment for experimental malignant glioma. J Neurooncol 80:9-17
Legnani, Federico G; Pradilla, Gustavo; Thai, Quoc-Anh et al. (2006) Lactacystin exhibits potent anti-tumor activity in an animal model of malignant glioma when administered via controlled-release polymers. J Neurooncol 77:225-32
Li, Yawen; Ho Duc, Hong Linh; Tyler, Betty et al. (2005) In vivo delivery of BCNU from a MEMS device to a tumor model. J Control Release 106:138-45
Sorg, Brian S; Peltz, Cathryn D; Klitzman, Bruce et al. (2005) Method for improved accuracy in endogenous urea recovery marker calibrations for microdialysis in tumors. J Pharmacol Toxicol Methods 52:341-9
Li, Yawen; Shawgo, Rebecca S; Tyler, Betty et al. (2004) In vivo release from a drug delivery MEMS device. J Control Release 100:211-9
Grossi, Peter M; Ochiai, Hidenobu; Archer, Gary E et al. (2003) Efficacy of intracerebral microinfusion of trastuzumab in an athymic rat model of intracerebral metastatic breast cancer. Clin Cancer Res 9:5514-20

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