Therapeutic and Biologic Studies in a Murine Model of NF1
Abstract
This report describes progress made during the second year of support for a translational research project involving Nfl mutant mice with myeloid leukemia. Progress made during the first year is also reviewed to provide essential background. This study has two Technical Objectives. First, examining the therapeutic efficacy of two agents (1) mycophenolate mofetiel (MM) and, (2) a fusion toxin that targets the GM-CSF receptor. 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. We are continuing correlative biochemical studies to elucidate the effects of these therapeutics on cellular GTP levels and Ras signaling. We produced and purified a GM-CSF immunotoxin during year 1 and have tested this in vitro. These studies surprisingly revealed agonist (rather than inhibitory effects) of the conjugate, and we have been working to discern the basis for this. In aim 2, we are utilizing Nfl mice to extend clinical observations suggesting that individuals with NFl are susceptible to the development of therapy-associated second cancers. These studies were initiated in year 1 and are progressing well. We are collecting tissues from mice with leukemia and will perform other correlative molecular studies over the next year. We anticipate that the proposed experiments will yield novel data that may be of practical value to patients with NFl and their physicians.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2000
- Accession Number
- ADA387816
Entities
People
- Kevin Shannon
Organizations
- University of California, San Francisco