Therapeutic and Biologic Studies in a Murine Model of NF1
Abstract
This final report describes the outcome of a translational research project involving Nf1 mutant mice with myeloid leukemia. Progress made during the full period of support is reviewed concisely and a final summary is provided. This research study pursued two Technical Objectives. First, the therapeutic efficacy of two agents: (1) mycophenolate mofetiel (MM) and, (2) a fusion toxin that targets the UM-CSF receptor was examined. These compounds represent rational new approaches for treating NF1-associated tumors. MM has been tested in the mouse model and our preliminary data indicate that it is unlikely to provide benefit to NF1 patients. However, biochemical studies demonstrated the predicted inhibitory effects on signaling through downstream effectors of Ras-GTP. We produced and purified a GM-CSF immunotoxins and tested an number of these in vitro. These studies surprisingly revealed agonist (rather than inhibitory effects) of the conjugates. The investigators are continuing to develop improved reagents. In aim 2, utilized NF1 mutant mice to extend clinical observations suggesting that individuals with NF1 are susceptible to the development of therapy-associated second cancers. These studies demonstrated dramatic cooperation between heterozygous inactivation of NF1 and exposure to mutagens in cancer development.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2001
- Accession Number
- ADA400468
Entities
People
- Kevin M. Shannon
Organizations
- University of California, San Francisco