SK 708/727. Protection of Bone Marrow from Toxicity to Chemotherapeutic Agents

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. 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 clinical trials. Mutant TS is also resistant to D1694 (Raltitrexed), 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
• 6,887,467
• 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