University of South Alabama Press Release

University of South Alabama, Office of Public Relations

January 27, 2004
Contact: Melissa M. Bowden, (251) 460-7279 mbowden@usouthal.edu

USA Cancer Research Institute Hosts Prominent Gene Therapy Researcher, Friday, February 6

Professor Christopher Baum, M.D., Ph.D. of Hanover, Germany will present a seminar on Retroviral Transgenesis and Oncogenesis, Friday, February 6th at 2:00 p.m. in the COM Conference Room.

Dr. Baum is one of the major players in the field of development of retroviral vectors for gene therapy. The retroviral vectors engineered by his group to transduce somatic stem cells are now used worldwide in experimental and clinical gene therapy protocols. In 2002, Dr. Baum and his group discovered that retroviral gene marking could induce leukemia in mice by insertional mutagenesis (Li et al., Science, 296, 497, 2002). A few months later, the risk of mutagenesis was confirmed by the observation of two cases of leukemia in children cured of X-linked SCID by gene therapy in the French clinical trial of Cavazzana-Calvo and Fischer.

Prof. Christopher Baum, M.D., Ph.D.
Title of the seminar: "RetroviralTransgenesis and Oncogenesis"
Host: Cancer Institute (Dr. Rappa/Dr. Lorico)

A partial list of his scientific publications follows:

Baum C, Hegewisch-Becker S, Eckert H-G, Stocking C, Ostertag W. Novel retroviral vectors for efficient expression of the multidrug-resistance (mdr-1) gene in early hemopoietic cells. Journal of Virology 69: 7541-7547 (1995)

Baum C, Eckert H-G, Stocking C, Ostertag W (1996) Activity of Friend mink cell focus-forming viruses during myelo-erythroid hematopoiesis. Experimental Hematology 24: 364-370

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, 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 Sp1 in the upstream control region and by a unique enhancer core creating an exclusive target for PEBP/CBF. Journal of Virology 71:6323-6331

Hildinger M, Fehse B, Hegewisch-Becker S, John J, Rafferty JA, Ostertag W, Baum C (1998) Dominant selection of hematopoietic progenitor cells with retroviral mdr1- coexpression vectors. Human Gene Therapy 9:33-42

Fischer N, Heinkelein M, Lindemann D, Enssle J, Baum C, Werder E, Zentgraf H, Müller JG, Rethwilm A (1998) Foamy virus particle formation. Journal of Virology 72:1610-1615
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 Therapy 5:1575-1579

Hildinger M, Schilz A, Eckert HG, Fehse B, Bohn W, Zander AR, Ostertag W, Baum C (1999) Bicistronic retroviral vectors for combining myeloprotection with cell surface marking. Gene Therapy 6:1222-1230

Hildinger M, Abel KL, Ostertag W, Baum C (1999) Design of 5’ untranslated sequences in retroviral vectors developed for medical use. Journal of Virology 73:4083-4089

Delecluse H-J, Pich D, Hilsendegen T, Baum C, Hammerschmidt W (1999) A first generation packaging cell line for Epstein-Barr Virus derived vectors. Proceedings of the National Academy of Sciences USA 96:5188-5193

Jelinek J, Rafferty JA, Cmejla R, Hildinger M, Chinnasamy D, Ostertag W, Margison GP, Dexter TM, Fairbairn LJ, Baum C (1999) A novel dual function retrovirus expressing multidrug resistance-1 and O6-alkylguanine-DNA-alkytransferase for engineering resistance of haemopoietic progenitor cells to multiple chemotherapeutic agents. Gene Therapy 6:1489-1493

Miletic H, Bruns M, Tsiakis K, Vogt B, Baum C, Rezai R, Kühlcke K, Cosset F-L, Ostertag W, Lother H, von Laer D (1999) Retroviral vectors pseudotyped with lymphocytic choriomeningitis virus. Journal of Virology 73:6114-6116

Schambach A, Wodrich H, Hildinger M, Bohne J, Krauesslich HG, Baum C (2000) Context-dependence of different modules for post-transcriptional enhancement of gene expression from retroviral vectors. Molecular Therapy, 2:435-445.

Turner SD, Rafferty JA, Fairbairn LJ, Asby J, Tinwell H, Eckert HG, Baum C, Lashford LS (2000) The effects of dose, route of administration, drug scheduling and MDR-1 gene transfer on the genotoxicity of etoposide in the bone marrow. Leukemia 14:1796-1802
Fehse B, Richters A, Putimtseva-Scharf K, Klump H, Li Z, Ostertag W, Zander AR, Baum C (2000) CD34 splice-variant : an attractive marker for selection of gene-modified cells. Molecular Therapy 1:448-456

Schilz A, Schiedlmeier B, Kuehlcke K, Fruehauf S, Lindemann C, Zeller WJ, Grez M, Fauser AA, Baum C, Eckert HG (2000) Retroviral-mediated MDR1 gene transfer into NOD/SCID repopulating hematopoietic cells under clinically relevant conditions. Molecular Therapy 2:609-618.

Wahlers A, Schwieger M, Li Z, Meier-Tackmann D, Lindemann C, Eckert HG, von Laer D, Baum C (2001) Influence of multiplicity of infection and protein stability on retroviral vector-mediated gene expression in hematopoietic cells. Gene Therapy 8:477-486.

Klump H, Schiedlmeier B, Vogt B, Ryan M, Ostertag W, Baum C (2001) Retroviral vector-mediated expression of HOXB4 in hematopoietic cells using a novel coexpression strategy. Gene Therapy 8:811-817.

Knipper R, Schiedlmeier B, Kuehlcke K, Lindemann C, Schilz A, Fruehauf S, Hildinger M, Ostertag W, Fauser AA, Baum C (2001) Improved post-transcriptional processing of an MDR1-retrovirus elevates expression of multidrug resistance in primary human hematopoietic cells. Gene Therapy 8:239-246.

Rappa G, Lorico A, Hildinger M, Fodstad O, Baum C (2001) Novel bicistronic retroviral vector expressing ÿ-glutamyl cysteine synthetase and the multidrug resistance protein 1 (MRP1) protects cells from MRP1-effluxed drugs and alkylating agents. Human Gene Therapy 12:1785-1796.

Baum C (2002) Gene therapy for inherited disorders of haematopoietic cells. The Hematology Journal 3: S148-153.

Wahlers A, Schwieger M, Zipfel P, Ostertag W, Baum C (2002) In vivo analysis of retroviral enhancer mutations in hematopoietic cells: SP1/EGR1 and ETS/GATA motifs contribute to LTR specificity. Journal of Virology 76: 303-312.

Carpinteiro A, Peinert S, Ostertag W, Zander AR, Hossfeld DK, Kuehlcke K, Eckert HG, Baum C, Hegewisch-Becker S (2002) Genetic protection of repopulating hematopoietic cells with an improved MDR1-retrovirus allows administration of intensified consolidation chemotherapy following stem cell transplantation. International Journal of Cancer 98: 785-792.

Li Z, Düllmann J, Schiedlmeier B, M. Schmidt M, von Kalle C, Meyer J, Forster M, Stocking C, Ostertag W, Wahlers A, Frank O, Kuehlcke K, Eckert HG, Fehse B, Baum C (2002) Murine leukemia induced by retroviral gene marking. Science 296:497.

Wahlers A, Kustikova O, Zipfel PF, Itoh K, Koester M, Heberlein C, Li Z, Schieldmeier B, Skerka C, Ostertag W, Baum C (2002) Upstream conserved sequences of mouse leukemia viruses are important for high transgene expression in lymphoid and hematopoietic cells. Molecular Therapy 6:313-320.

Fehse B, Koustikova O, Li Z, Wahlers A, Beyer W, Chalmers D, Tiberghien P, Zander AR, Baum C (2002) A novel “sort-suicide” fusion gene vector for T cell manipulation. Gene Therapy, 9:1633-1638.

Lorico A, Bertola A, Baum C, Fodstad O, Rappa G (2002) Role of the Multidrug Resistance Protein 1 in protection from heavy metal oxyanions: investigations in vitro and in MRP1-deficient mice. Biochemical Biophysical Research Communications, 291:617-622

Rappa G Gamszik MP, Mitina RL, Baum C, Fodstad O, Lorico A (2003) Retroviral transfer of MRP1 and gamma-glutamyl cysteine synthetase modulates cell sensitivity to L-buthionine-S,R-sulphoximine (BSO): new rationale for the use of BSO in cancer therapy. European Journal of Cancer 39:120-128.

Li Z, Schwieger M, Lange C, Kraunus J, Sun H, von den Akker E, Modlich U, Serinsöz E, Will E, von Laer D, Stocking C, Fehse B, Schiedlmeier B, Baum C (2003) Predictable and efficient retroviral gene transfer into murine bone marrow repopulating cells using a defined vector dose. Experimental Hematology, 31: 1206-1214.

Kraunus J, Schaumann DHS, Meyer J, Modlich U, Klump H, Baum C (2003) Self-inactivating retroviral vectors with improved RNA processing. Gene Therapy, in press.

Baum C, Düllmann J, Li Z, Fehse B, Meyer J, Williams DA, von Kalle C (2003) Side effects of retroviral gene transfer into hematopoietic stem cells. Blood 101:2099-2114.

Baum C, Fehse B (2003) Mutagenesis by retroviral transgene insertion: Risk assessment and potential alternatives. Current Opinion in Molecular Therapeutics 5:458-462

Williams DA, Baum C (2003) Gene Therapy – New Challenges ahead. Science 302:400-401.
Baum C, von Kalle C, Stall FJT, Li Z, Fehse B, Schmidt M, Weerkamp F, Karlsson S, Wagemaker S, Williams D (2003) Chance or necessity? Insertional mutagenesis in gene therapy and its consequences. Molecular Therapy, in press. Baum C (2003) Gene therapy: take five? Blood 101:1209.

Baum C, von Kalle C (2003) Gene therapy targeting hematopoietic cells: Better not leave it to chance. Acta Haematologica 110:107-109 Klein C, Baum C (2003) Gene therapy for inherited disorders of haematopoietic cells. The Hematology Journal, in press.

For more information contact Melissa Bowden, (251) 460-7279. mbowden@usouthal.edu