Engraftment of MDR1 and NeoR gene-transduced hematopoietic cells after breast cancer chemotherapy

To determine whether the multidrug resistance gene MDR1 could act as a sele ctable marker in human subjects, we studied engraftment of peripheral blood progenitor cells (PBPCs) transduced with either MDR1 or the bacterial NeoR gene in six breast cancer patients. This study differed from previous MDR1 gene therapy studies in that patients received only PBPCs incubated in ret roviral supernatants (no nonmanipulated PBPCs were infused), transduction o f PBPCs was supported with autologous bone marrow stroma without additional cytokines, and a control gene (NeoR) was used for comparison with MDR1. Tr ansduced PBPCs were infused after high dose alkylating agent therapy and be fore chemotherapy with MDR substrate drugs. We found that hematopoietic rec onstitution can occur using only PBPCs incubated ex vivo, that the MDR1 gen e product may play a role in engraftment, and that chemotherapy may selecti vely expand MDR1 gene transduced hematopoietic cells relative to NeoR trans duced cells in some patients. This is a US government work. There are no restrictions on its use.