Methods for producing differentiated cells from immature hematopoietic cells
Patent 5648248 Issued on July 15, 1997. Estimated Expiration Date: January 25, 2015. Estimated Expiration Date is calculated based on simple USPTO term provisions. It does not account for terminal disclaimers, term adjustments, failure to pay maintenance fees, or other factors which might affect the term of a patent.
The present invention concerns methods for producing differentiated cells from immature hematopoietic cells. Preferably, a gene coding for a conditional v-rel estrogen receptor fusion protein, v-relER, that causes estrogen-dependent but otherwise unaltered v-rel-specific transformation, is introduced into bone marrow cells. Following inactivation of v-relER oncoprotein activity by administration of an estrogen antagonist, cells differentiate into antigen-presenting dendritic cells as judged by several morphological and functional criteria. Additionally, under different culture conditions, v-relER cells differentiate into cells resembling polymorphonuclear neutrophils. The invention further concerns differentiated cells obtained by the claimed method as well as their use for screening of potentially immunomodulatory substances and in the development of vaccines.
Other References
Ballard et al., "The v-rel Oncogene Encodes a .kappa.B Enhancer Binding Protein That Inhibits NF-.kappa.B Function," Cell 63:803-814 (1990)
Barth et al., "Reticuloendotheliosis Virus REV-T (REV-A)-Induced Neoplasia: Development of Tumors within the T-Lymphoid and Myeloid Lineages," J. Virol. 64(12) : 6054-6062 (1990)
Beug, H. and Graf, T., "Co-operation between viral oncogenes in avian erythroid and myeloid leukaemia," Eur. J. Clin. Invest. 19:491-502 (1989)
Beug et al., "Hematopoietic Cells Transformed in Vitro by REVT Avian Reticuloendotheliosis Virus Express Characteristics of Very Immature Lymphoid Cells," Virology 115:295-309 (1981)
Boehmelt et al., "Hormone-regulated v-rel estrogen receptor fusion protein: reversible induction of cell transformation and cellular gene expression," EMBO J. 11(12):4641-4652 (1992)
Bose, Jr., H.R., "The Rel family: models for transcriptional regulation and oncogenic transformation," Chimica et Biophysica Acta 1114:1-17 (1992)
Bowler et al., "Novel Steroidal Pure Antiestrogens," Steroids 54(1) :71-99 (1989)
Burk, O. and Klempnauer, K.H., "Estrogen-dependent alterations in differentiation state of myeloid cells caused by a v-myb/estrogen receptor fusion protein," EMBO J. 10(12) :3713-3719 (1991)
Capobianco, A.J., and Gilmore, T.D., "A Conditional Mutant of vRel Containing Sequences from the Human Estrogen Receptor," Virology 193:160-170 (1993)
Eilers et al., "Chimaeras of Myc oncoprotein and steroid receptors cause hormone-dependent transformation of cells," Nature 340:66-68 (1989)
Inaba et al., "Generation of Large Numbers of Dendritic Cells from Mouse Bone Marrow Cultires Supplemented with Granulocyte/Macrophage Colony-stimulating Factor," J. Exp. Med. 176:1693-1702 (1992)
Inaba et al., "Granulocytes, macrophages, and dendritic cells arise from a common major histocompatibility complex class II-negative progenitor in mouse bone marrow," PNAS USA 90:3038-3042 (1993)
Jackson et al., "Hormone-conditional transformation by fusion proteins of c-Abl, and its transforming variants" EMBO J. 12(7) :2809-2819 (1993)
Louvion et al., "Fusion of GAL4-VP16 to a steroid-binding domain provides a tool for gratuitous induction of galactose-responsive genes in yeast," Gene 131:129-134 (1993)
Paglia et al., "Immortalized Dendritic Cell Line Fully Competent in Antigen Presentation Primary T Cell Responses In Vivo," J. Exp. Med. 178:1893-1901 (1993)
Picard et al., "A Movable and Regulable Inactivation Function within the Steroid Binding Domain of the Glucocorticoid Receptor," Cell 54:1073-1080 (1988)
Radke et al., "Transformation of Both Erythroid and Myeloid Cells by E26, an Avian Leukemia Virus That Contains The myb Gene," Cell 31:643-653 (1982)
Romani et al., "Proliferating Dendritic Cell Progenitors in Human Blood," J. Exp. Med. 180:83-93 (1994)
Sallusto, F. and Lanzavecchia, A., "Efficient Presentation of Soluble Antigen by Cultured Human Dendritic Cells Is Maintained by Granulocyte/Macrophage Colony-stimulating Factor Plus Interleukin 4 and Downregulated by Tumor Necrosis Factor , " J. Exp. Med. 179:1109-1118 (1994)
Scherrer et al., "Evidence that the Hormone Binding Domain of Steroid Receptors Confers Hormonal Control on Chimeric Proteins by Determining Their Hormone-Regulated Binding to Heat-Shock Protein 90," Biochemistry 32:5381-5386 (1993)
Superti-Furga et al., "Hormone-dependent transcriptional regulation and cellular transformation by Fos-steroid receptor fusion proteins," PNAS USA 88:5114-5118 (1991)
Umek et al., "CCAAT-Enhancer Binding Proteins: A Component of a Differentiation Switch," Science 251:288-292 (1991)
White, D.W. and Gilmore, T.D., "Temperature-Sensitive Transforming Mutants of the v-rel Oncogene," J. Virology 67:6876-6881 (1993)
Zenke et al., "v-erbA Specifically Suppresses Transcription of the Avian Erythrocyte Anion Transporter (Band 3) Gene," Cell 52:107-119 (1988)
Zhang et al., "The v-rel Oncogene of Avian Reticuloendotheliosis Virus Transforms Immature and Mature Lymphoid Cells of the B Cell Lineage in Vitro," Virology 183:457-466 (1991)
Boehmelt, G., et al., "A hormone-inducible v-rel estrogen receptor fusion as a means to transform early hematopoietic progenitor cells and to study their differentiation pathway," Avian Immunol. Prog. 62:337-341 (Aug.-Sep. 1993)
Boehmelt, G., et al., "Dendritic Cell Progenitor Is Transformed by a Conditional v-Rel Estrogen Receptor Fusion Protein v-ReLER," Cell 80:341-352 (Jan. 27, 1995
January 25, 2015. Estimated Expiration Date is calculated based on simple USPTO term provisions. It does not account for terminal disclaimers, term adjustments, failure to pay maintenance fees, or other factors which might affect the term of a patent.
