Effectiveness of Bispecific Cytotoxin (DTEGFATF) in Ameliorating Human Glioblastoma Tumors

Travis Spangler2008-2009

Research Problem

http://upload.wikimedia.org/wikipedia/commons/c/c0/Glioblastoma_-_MR_sagittal_with_contrast.jpg

Background: Stish et al. (2007)

Diphtheria toxin epidermal growth factor 13

DTEGF13

DTEGF13

DTEGFIL13DTIL13

Diphtheria toxin amino acid transfer

Diphtheria toxin epidermal growth factor

Background: Stish et al. (2007)

Diphtheria toxin epidermal growth factor 13

DTEGF13

DTEGFATF ATF

Diphtheria toxin epidermal growth factor amino terminal fragment

DTEGFATF ATF

DTEGFATFDTAT

Diphtheria toxin amino acid transfer

Diphtheria toxin epidermal growth factor

Background: Stish et al. (2008)

DTEGF

Background: Stish et al. (2008)

DTEGF

Background: Vallera et al. (2002)

DTAT

Background: Vallera et al. (2002)

DTAT

http://www.biooncology.com/bioonc/images/her-main.jpg

Receptor

http://www.biooncology.com/bioonc/images/her-main.jpg

Receptor

Receptor

Receptor

Receptor ReceptorReceptor

Receptor

Receptor

Receptor

• DTEGFATF• DTEGF• DTAT

• DTEGFATF• DTEGF• DTAT• DTEGF + DTAT

Cell Lines

U-87 HUVEC HPB-MLT

http://www.assaysoft.com/gallery/02Microscopy/MicroscopyGallery/12/Human%20Umbilical%20Vein%20Endothelial%20Cells%20(HUVEC).jpghttp://data-integrator.com

http://www.hpb.org.uk/userimages/panfigure2.jpg

Cell Lines

U-87 HUVEC HPB-MLT

http://www.assaysoft.com/gallery/02Microscopy/MicroscopyGallery/12/Human%20Umbilical%20Vein%20Endothelial%20Cells%20(HUVEC).jpghttp://data-integrator.com

http://www.hpb.org.uk/userimages/panfigure2.jpg

Cell Lines

U-87 HUVEC HPB-MLT

http://www.assaysoft.com/gallery/02Microscopy/MicroscopyGallery/12/Human%20Umbilical%20Vein%20Endothelial%20Cells%20(HUVEC).jpghttp://data-integrator.com

http://www.hpb.org.uk/userimages/panfigure2.jpg

Cell Lines

U-87 HUVEC HPB-MLT

http://www.assaysoft.com/gallery/02Microscopy/MicroscopyGallery/12/Human%20Umbilical%20Vein%20Endothelial%20Cells%20(HUVEC).jpghttp://data-integrator.com

http://www.hpb.org.uk/userimages/panfigure2.jpg

Proliferation Assays

Proliferation Assays

Proliferation Assays

Proliferation Assays

Proliferation Assays

Proliferation Assay Results

Proliferation Assay Results

Proliferation Assay Results

Proliferation Assay Results

Proliferation Assay Results

Proliferation Assay Results

Proliferation Assay Results

Blocking Assay

http://www.biooncology.com/bioonc/images/her-main.jpg

Blocking Assay

http://www.biooncology.com/bioonc/images/her-main.jpg

Blocking Assay

DTEGFATF

http://www.biooncology.com/bioonc/images/her-main.jpg

DTEGFATF

DTEGFATF

DTEGFATF DTEGFATF DTEGFATFDTEGFATF

DTEGFATF

DTEGFATF

DTEGFATF

Blocking Assay

http://www.biooncology.com/bioonc/images/her-main.jpg

Blocking Assay Results

Blocking Assay Results

Limitations

• Blocking assay– Bispecific cytotoxin disperses throughout tumors– Concentration of antibodies

Future Work

• Clinical trial

Acknowledgements• Dr. Daniel Vallera• The University of Minnesota• Vallera Lab• Lois Fruen• Advanced Science Research

Effectiveness of Bispecific Cytotoxin (DTEGFATF) in Ameliorating Human Glioblastoma Tumors

Travis Spangler2008-2009