New Experimental Approaches to the Adoptive Immunotherapy of Cancer: Cytokines, Gene Therapy, Oncogenes and Transgenic Mice

Author(s):  
B. A. Fox
Biotherapy ◽  
1992 ◽  
Vol 5 (2) ◽  
pp. 119-129 ◽  
Author(s):  
Gilda G. Hillman ◽  
Gabriel P. Haas ◽  
Werner H. Wahl ◽  
Denis M. Callewaert

2006 ◽  
pp. 181-212
Author(s):  
Peter A. Cohen ◽  
Mohamed Awad ◽  
Suyu Shu

2004 ◽  
pp. 153-158
Author(s):  
A. Tiede ◽  
M. Eder ◽  
M. Scherr ◽  
A. Ganser ◽  
M. von Depka Prondzinski

2009 ◽  
Vol 50 ◽  
pp. S214-S215
Author(s):  
L. Vanrell ◽  
C. Olague ◽  
A. Vales ◽  
A. Pañeda ◽  
L. Tenembaum ◽  
...  

2008 ◽  
Vol 4 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Li Zhang ◽  
Pouneh Dokouhaki

Blood ◽  
2000 ◽  
Vol 95 (10) ◽  
pp. 3242-3249 ◽  
Author(s):  
Joel E. Rubin ◽  
Peter Pasceri ◽  
Xiumei Wu ◽  
Philippe Leboulch ◽  
James Ellis

Abstract The human β-globin locus control region (LCR) contains chromatin opening and transcriptional enhancement activities that are important to include in β-globin gene therapy vectors. We previously used single-copy transgenic mice to map chromatin opening activity to the 5′HS3 LCR element. Here, we test novel hybrid globin genes to identify β-globin gene sequences that functionally interact with 5′HS3. First, we show that an 850-base pair (bp) 5′HS3 element activates high-level β-globin gene expression in fetal livers of 17 of 17 transgenic mice, including 3 single-copy animals, but fails to reproducibly activate Aγ-globin transgenes. To identify the β-globin gene sequences required for LCR activity by 5′HS3, we linked the 815-bp β-globin promoter to Aγ-globin coding sequences (BGT34), together with either the β-globin intron 2 (BGT35), the β-globin 3′ enhancer (BGT54), or both intron 2 and the 3′ enhancer (BGT50). Of these transgenes, only BGT50 reproducibly expresses Aγ-globin RNA (including 7 of 7 single-copy animals, averaging 71% per copy). Modifications to BGT50 show that LCR activity is detected after replacing the β-globin promoter with the 700-bp Aγ-globin promoter, but is abrogated when an AT-rich region is deleted from β-globin intron 2. We conclude that LCR activity by 5′HS3 on globin promoters requires the simultaneous presence of β-globin intron 2 sequences and the 260-bp 3′ β-globin enhancer. The BGT50 construct extends the utility of the 5′HS3 element to include erythroid expression of nonadult β-globin coding sequences in transgenic animals and its ability to express antisickling γ-globin coding sequences at single copy are ideal characteristics for a gene therapy cassette.


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