Scientific Abstract 
A ONE-PAGE SCIENTIFIC ABSTRACT OF THE PROTOCOL : 
We propose a protocol to transduce human bone marrow cells with 
the multiple drug resistance (MDR) gene. This is done to 
increase the expression of MDR in human bone marrow cells that 
usually express very low levels of this important glycoprotein. 
High MDR-producing marrow cells are necessary to prevent killing 
of these cells with several classes of chemotherapeutic agents, 
including taxol, anthracyclines, vinca-alkaloids, and etoposides. 
Usually, when high doses of chemotherapeutic agents including 
those mentioned above are employed, significant bone marrow 
toxicity is induced. To avoid this toxicity, autologous bone 
marrow transplantation (ABMT) (the removal of human bone marrow 
and its reinfusion) is done in association with the 
administration of high-dose chemotherapy for patients with 
advanced cancer. 
The transduction of the removed bone marrow cells by a retrovirus 
containing the MDR gene is proposed. These transduced cells will 
be reinfused into patients as is ordinarily done in ABMT with 
high-dose chemotherapy. It is hoped that the expression of MDR 
in the transduced bone marrow cells will induce resistance of 
these cells to the toxic effects of subsequent chemotherapy. A 
safe and efficient line of cells producing a retrovirus efficient 
in transferring the MDR gene into animal bone marrow cells will 
be used in this study and is expected to have no toxicity. The 
potential benefit of the protocol is that it may create a 
population of human bone marrow cells resistant to the toxicity 
of high-dose chemotherapy with drugs such as taxol, an MDR- 
responsive agent in patients with advanced breast and ovarian 
cancers, and either allow these patients to receive higher doses 
of taxol or allow patients to be treated with taxol who could not 
tolerate this therapy because of its bone marrow toxicity. If 
this treatment is successful, it could be used to administer 
higher dose chemotherapy to patients undergoing ABMT at earlier 
times and increase the possibility of prolonged survival or cure 
in these patients. 
Recombinant DNA Research, Volume 18 
[91] 
