RETROVIRAL GENE TRANSDUCTION OF CIRCULATING PROGENITOR CELLS IN PATIENTS WITH METASTATIC BREAST-CANCER

被引：11

作者：

COLES, RE ^{[1
]}

BOYLE, TJ ^{[1
]}

KURTZBERG, J ^{[1
]}

STEWART, A ^{[1
]}

PETERS, WP ^{[1
]}

LYERLY, HK ^{[1
]}

机构：

[1] DUKE UNIV,MED CTR,DEPT SURG PEDIAT,BOX 3551,DURHAM,NC 27710

来源：

SURGICAL ONCOLOGY-OXFORD | 1993年 / 2卷 / 01期

关键词：

BREAST CANCER; CD34; GENE THERAPY; RETROVIRAL VECTOR; STEM CELL; TRANSDUCTION;

D O I：

10.1016/0960-7404(93)90038-Z

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：1 / 6

页数：6

共 15 条

[1] Corey, DeSilva, Holland, Et al., Serial transplantations of methotrexate-resistance bone marrow: protection of murine recipients from drug toxicity by progeny of transduced stem cells, Blood, 75, pp. 337-343, (1990)
[2] Galski, Sullivan, Willingham, Et al., Expression of a human multidrug resistance cDNA (MDRI) in the bone marrow of transgenic mice, Mol Cell Biol, 9, pp. 4357-4363, (1989)
[3] Keith, Brown, Pragnell, Retrovirus mediated transfer and expression of GM-CSF in haematopoietic cells, British Journal of Cancer, 62, pp. 288-294, (1990)
[4] Gutierrez, Lemoine, Sikora, Gene therapy for cancer, Lancet, 339, pp. 715-721, (1992)
[5] Golde, The stem cell, Scientific American, 265, 6, pp. 86-93, (1991)
[6] Miller, Rosman, Improved retroviral vectors for gene transfer and expression, Biotechniques, 7, 9, pp. 980-982, (1989)
[7] Miller, Retrovirus packaging cells, Hum Gene Ther, 1, 1, pp. 5-14, (1990)
[8] Sambrook, Fritsch, Maniatis, Molecular Cloning: A Laboratory Manual, (1989)
[9] Miller, Miller, Miller, Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection, Mol Cell Biol, 10, 8, pp. 4239-4242, (1990)
[10] Innis, Gelfand, Sninsky, Et al., PCR Protocols: A Guide to Methods and Applications, (1990)

← 1 2 →