Retroviral gene transduction of circulating progenitor cells in patients with metastatic breast cancer.
The use of somatic gene therapy for the treatment of breast cancer has many potential applications. Because chemotherapeutic protocols for breast cancer are commonly limited by bone marrow toxicity, transduction of genes into pleuripotent stem cells may allow the generation and maintenance of immune responses in the presence of lymphocytotoxic agents. The practical utility of stem cell isolation and transduction would be enhanced if stem cells circulating in the peripheral blood could be isolated in patients, however this approach has been limited by the small numbers of such cells in the circulation. In these studies, recombinant granulocyte colony stimulating factor (G-CSF) was administered to patients with metastatic breast cancer to increase the number of circulating stem cells. Stem cells in the peripheral blood were then isolated and a retroviral vector (LXSN) was used to transduce the neomycin phosphotransferase gene into these cells. Gene transduction was demonstrated by resistance to the toxic effects of a neomycin analog (G418) and the detection of retroviral DNA from transduced cells. A practical method of transfer of exogenous genes into the circulating pleuripotent stem cells of patients with metastatic breast cancer is documented by these experiments. Application of these findings may allow the generation of cells resistant to anti-neoplastic agents or unique lymphoid effector cells with potent immune functions for the treatment of patients with metastatic breast cancer.
Coles
R E
RE
Department of Surgery, Duke University Medical Center, Durham, NC 27710.
Boyle
T J
TJ
Kurtzberg
J
J
Stewart
A
A
Peters
W P
WP
Lyerly
H K
HK
D001483:Base Sequence; D001943:Breast Neoplasms / Q000276:immunology / Q000628:therapy*; D004247:DNA / Q000032:analysis; D004351:Drug Resistance / Q000235:genetics / Q000276:immunology; D005260:Female; D015967:Gene Expression Regulation, Viral; D015316:Genetic Therapy; D005822:Genetic Vectors; D005839:Gentamicins / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012190:Retroviridae / Q000235:genetics; D013234:Stem Cells / Q000187:drug effects* / Q000276:immunology; D014162:Transfection
D005839:Gentamicins; D004247:DNA; C010680:antibiotic G 418