Summary of Invention
This invention is a method to protect bone marrow from toxicity to certain chemotherapeutic agents, specifically inhibitors of dihydrofolate reductase (DHFR) or thymidylate synthase (TS).
Genes encoding mutant forms of human DHFR and human TS provide protection of hemotopoietic progenitor cells to inhibitors of DHFR or TS enzymes. Transduction of hematopoietic cells with these genes will allow the use of higher doses of chemotherapeutic drugs, improving the efficacy of the drugs and reducing damage to bone marrow cells.
Advantages
- Transduction of hematopoietic cells with drug-resistant genes is a promising new application, which has already entered into clinical trials. It has a clear advantage over currently available measures to restore hematopoiesis after chemotherapy, such as autologous stem cell reinfusion and/or hematopoietic growth factor support.
- The mutant DHFR is resistant to Methotrexate.
- The mutant TS is resistant to AG337, an anticancer drug currently in Phase III clinical trials. It is also resistant to D1694, an anticancer drug that is currently in use in Europe and in Canada.
Areas of Application
Cell therapy.
Stage of Development
Phase I clinical trials planned.
Lead Inventor
Dr. Joseph R. Bertino
Patent Information
US patents 6,416,987 and 6,642,043.
References
Ercikan-Abali EA, et al. Cancer Res. 56:4142-5 (1996).
Contact Information
Jeffrey Horenstein, PhD
Tel: 212-639-6181; Fax: 212-717-3439
E-mail: horenstj@mskcc.org
