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Elizabeth M Hadac, Elizabeth J Kelly, Stephen J Russell 

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Presentation on theme: "Elizabeth M Hadac, Elizabeth J Kelly, Stephen J Russell "— Presentation transcript:

1 Myeloma Xenograft Destruction by a Nonviral Vector Delivering Oncolytic Infectious Nucleic Acid 
Elizabeth M Hadac, Elizabeth J Kelly, Stephen J Russell  Molecular Therapy  Volume 19, Issue 6, Pages (June 2011) DOI: /mt Copyright © 2011 The American Society of Gene & Cell Therapy Terms and Conditions

2 Figure 1 Characterization of coxsackievirus A21 (CVA21) RNA by electrophoresis and assessment of viral production. (a) RNA Flash Gel with molecular weight (kb) markers (left) and CVA21 transcript (right). (b) Time-course of virus production in H1-HeLa cells transfected with CVA21 RNA. TCID50, tissue culture infectious dose 50. Molecular Therapy  , DOI: ( /mt ) Copyright © 2011 The American Society of Gene & Cell Therapy Terms and Conditions

3 Figure 2 In vivo demonstration of tumor response to intratumorally injected coxsackievirus A21 (CVA21) RNA. Tumor volumes of SCID mice carrying subcutaneous Kas6/1 human myeloma xenografts were treated with (a) 106 TCID50 CVA21 virus (n = 3), (b) Opti-MEM control (n = 8), (c) 20 µg CVA21 RNA (n = 7) or (d) 20 µg CVA21 RNA treated with 60 µg RNaseA (n = 2). Based on the segmented model, there was no overall group effect (P = 0.16) or group effect prior to day 6 (P = 0.49). There was, however, a significant effect after day 6 (P < ) with reductions of tumor volume in the RNA (P < ) and virus (P < ) groups compared to the control group. There was no after day 6 difference in the RNA + Rnase group compared to the control group (P = 0.29). MEM, minimal essential medium. Molecular Therapy  , DOI: ( /mt ) Copyright © 2011 The American Society of Gene & Cell Therapy Terms and Conditions

4 Figure 3 Formalin-fixed paraffin-embedded tumor sections stained by hematoxylin and eosin. Microscopic images shows inflammation and necrosis in (a) coxsackievirus A21 (CVA21) virus and (b) CVA21 RNA treated tumors while the (c) Opti-MEM control and (d) CVA21RNA + RNaseA tumors are within normal limits. Bar = 0.1 mm. MEM, minimal essential medium. Molecular Therapy  , DOI: ( /mt ) Copyright © 2011 The American Society of Gene & Cell Therapy Terms and Conditions

5 Figure 4 In vivo dose–response of tumor regression following intratumoral treatment with coxsackievirus A21 (CVA21) RNA. Tumor volumes of SCID mice carrying subcutaneous Kas6/1 human myeloma xenografts were treated with (a) Opti-MEM control, (b) 1 µg, (c) 2 µg, (d) 4 µg, (e) 8 µg, (f) 16 µg, or (g) 32 µg CVA21 RNA. Mice with tumor progression (gray lines), mice with tumor regression (black lines). (h) Kaplan–Meier survival curves of control and RNA treated mice. Based on the segmented model, there was no overall dose effect (P = 0.19) or dose effect prior to day 10 (P = 0.20). There was, however, a significant dose effect after day 10 (P = ) showing increased dose was associated with decrease in tumor volume. This was confirmed when evaluating the after day 10 results in a separate model (P < ). MEM, minimal essential medium. Molecular Therapy  , DOI: ( /mt ) Copyright © 2011 The American Society of Gene & Cell Therapy Terms and Conditions


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