Abstract
Genes conferring resistance to anticancer drugs are expressed in hematopoietic cells to increase the therapeutic index of chemotherapy and to establish a system for dominant selection of gene-modified cells in vivo. We have developed powerful retroviral vectors for this approach. These vectors are known as Friend mink cell focus-forming/murine embryonic stem cells virus hybrid vectors (FMEV), characterised by mediating high constitutive transgene expression in hematopoietic cells. In our recent work, we have elaborated a new generation of FMEV expressing dominant selection markers like multidrug resistance 1 (MDR1) alone or in combination with other genes at further increased efficiency and safety.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Baum C, Margison G, Eckert H-G, Fairbairn L, Ostertag W, Rafferty J (1996) Gene transfer to augment the therapeutic index of anti-cancer chemotherapy. Gene Ther 3:1–3
Margison G, Hickson I, Jelinek J, Kelly J, Elder RH, Rafferty JA, Fairbairn LJ, Dexter TM, Stocking C, Baum C, Ostertag W, Donelly D, McMurry TBH, McCormick J, McElhinney RS (1996) Resistance to alkylating agents: more or less. Anti-Cancer Drugs 7:109–116
Zhao S-C, Banerjee D, Mineishi S, Bertino JR (1997) Post-transplant methotrexate administration leads to improved curability of mice bearing a mammary tumor transplanted with marrow transduced with a mutant human dihydrofolate reducatse cDNA. Hum Gene Ther 8:903–909
Cardarelli CO, Aksentijevich I, Pastan I, Gottesman MM (1995) Differential effects of P-glyco-protein inhibitors on NIH3T3 cells transfected with wild-type (G185) or mutant (V185) multidrug transporters. Cancer Res 55:1086–1091
Hickson I, Fairbairn LJ, Chinnasamy N, Dexter TM, Margison GP, Rafferty JA (1996) Protection of mammalian cells against chloroethylating agent toxicity by an 06-benzylguanine-resistant mutant of human 06-alkylguanine-DNA alkyltransferase. Gene Ther 3: 868–877
Magni M, Shammah S, Sciro R, Mellado W, Dalla-Favera R, Gianni AM (1996) Induction of cyclophosphamide-resistance by aldehyde-dehydrogenase gene transfer. Blood 87:1097–1103
Stocking C, Baum C (1997) Gene transfer into haematopoietic cells. In: :“Bailliere’s Clinical Haematology, Vol. 10: Molecular Haemopoiesis”, ed. by Whetton AD, Bailliere Tindall London, pp. 445–466
Baum C, Stocking C, Wagener T, Eckert H-G, Ostertag W (1997) Gene transfer and transgene expression in hematopoietic cells (Review). In Strauss M, Barranger JA (eds) Concepts in Gene Therapy. DeGruyter, Berlin, pp 233–266
Baum C, Ostertag W, Stocking C, von Laer D (1998) Retroviral vector design for cancer gene therapy. In Lattime E, Gerson S (eds) Seminars in oncology. Academic Press, San Diego, in press.
Laer von D, Thomsen S, Vogt B, Donath M, Kruppa J, Rein A, Ostertag W, Stocking C (1998) Entry of amphotropic and 10 Ai pseudotyped murine retroviruses is restricted in hematopoietic stem cell lines. J Virol 72:1424–1430
Naldini L, Blömer U, Gallay P, Ory D, Mulligan R, Gage FH, Verma IM, Trono D (1996) In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272:263–267
Conneally E, Eaves CJ, Humphries RK (1998) Efficient retroviral-m ediated gene transfer to human cord blood stem cells with in vivo repopulating potential. Blood 91:3487–3493
Hanenberg H, Xiao LX, Dilloo D, Hashino K, Kato I, Williams DA (1996) Colocalization of retrovirus and target cells on specific fibronactin fragments increases genetic transduction of mammalian cells. Nat Med 2:876–882
Baum C, Hegewisch-Becker S, Eckert H-G, Stocking C, Ostertag W (1995) Novel retroviral vectors for efficient expression of the multidrug-resistance (mdr-i) gene in early hemopoietic cells. J Virol 69:7541–7547
Eckert H-G, Stockschläder M, Just U, Hegewisch-Becker S, Grez M, Zander A, Ostertag W, Baum C (1996) High-dose multidrug resistance in primary human hematopoietic progenitor cells transduced with optimized retroviral vectors. Blood 88:3407–3415
Baum C, Eckert H-G, Stockschläder M, Just U, Hegewisch-Becker S, Hildinger M, Uhde A, John J, Ostertag W (1996) Improved retroviral vectors for hematopoietic stem cell protection and in vivo selection. J Hematother 5:323–329
Hildinger M, Eckert HG, Schilz AJ, John J, Ostertag W, Baum C (1998) FMEV vectors: both retroviral long terminal repeat and leader are important for high expression in transduced hematopoietic cells. Gene Ther, in press
Grez M, Akgun E, Hilberg F, Ostertag W (1990) Embryonic stem cell virus, a recombinant murine retrovirus with expression in embryonic stem cells. Proc Natl Acad Sci USA 87:9202–9206
Cheng L, Du C, Lavau C, Chen S, Tong J, Chen BP, Scollay R, Hawley RG, Hill B (1998) Sustained gene expression in retrovirally transduced, engrafting human hematopoietic stem cells and their lympho-myeloid progeny. Blood 92:83–92
Robbins PB, Yu XJ, Skelton DM, Pepper KA, Wasserman RM, Zhu L, Kohn DB (1997) Increased probability of expression from modified retroviral vectors in embryonal stem cells and embryonal carcinoma cells. J Virol 1:9466–9474
Hildinger M, Ostertag W, Abel KL, Baum C (1998) Ideal design of 5’ untranslated sequences in retroviral vectors: high and specific transgene expression with minimal potential for viral recombination. Submitted for publication
Jelinek J, Rafferty JA, Cmejla R, Hildinger M, Chinnasamy D, Ostertag W, Margison GP, Dexter TM, Fairbairn LJ, Baum C (1998) Transduction of human haemopoietic progenitor cells with a dual function retrovirus expressing multidrug resistance-i and 06-alkylguanine-DNA-alkytransferase confers resistance to multiple chemotherapeutic agents. Submitted for publication
Hildinger M, Fehse B, Hegewisch-Becker S, John J, Rafferty JA, Ostertag W, Baum C (1998) Dominant selection of hematopoietic progenitor cells with retroviral MDRi-coexpression vectors. Hum Gene Ther 9:33–42
Hildinger M, Fehse B, Bohn W, Zander AR, Ostertag W, Baum C (1998) Bicistronic retroviral vectors for combining myeloprotection with cell surface marking. Submitted for publication
Fielding AK, Maurice M, Morling FJ, Cosset FL, and Russell S (1998) Inverse Targeting of Retroviral Vectors: Selective Gene Transfer in a Mixed Population of Hematopoietic and Nonhematopoietic Cells. Blood 91:1802–1809
Baum C, Itoh K, Meyer J, Laker C, Ito Y, Ostertag W (1997) The potent enhancer activity of SFFVp in hematopoietic cells is governed by a binding site for Spi in the upstream control region and by a unique enhancer core creating an exclusive target for PEBP/CBF. J Virol 71:6323–633
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2000 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Baum, C., Hildinger, M., Ostertag, W. (2000). Retroviral Transfer and Expression of Drug Resistance Genes in Hematopoietic Cells. In: Berdel, W.E., et al. Transplantation in Hematology and Oncology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59592-9_34
Download citation
DOI: https://doi.org/10.1007/978-3-642-59592-9_34
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-64041-4
Online ISBN: 978-3-642-59592-9
eBook Packages: Springer Book Archive