Mechanism of lipopolyamine-induced immunotozin sensitization in cancer cells
Immunotoxins (ITx) represent a new, alternate class of therapeutic agent. ITx is made when the active part of a toxin is conjugated with the binding portion of an antibody that recognizes a cancer-specific antigen. The antibody component makes ITx highly specific, as it will only bind to cells displaying the correct surface antigen. This characteristic lowers the chance of nonspecific cell damage, which causes many of the severe side effects of other chemotherapeutics. The ITx we use is a conjugate of saporin toxin. Saporin is a ribosomal inhibiting protein derived from the plant Saponaria officinales, which kills the cell by inhibiting protein synthesis. ITx enters the cancer cell by binding to the cellular marker it is specific for on the cell surface. From there, it is endocytosed, compartmentalized in an endosome, and eventually escapes to the cytosol where its ribosomal target is located. Increasing the rate of escape to the cytosol is the key to increasing cell death. The mechanism by which saporin escapes the endosome and enters the cytosol is poorly understood. Two potential mechanisms involving the rupture of the endocytic vesicle were examined. Through experiments using large unilamellar vesicles as endosomal mimics, we have been able to characterize the mechanism by which saporin works to burst the endosomal membrane through RET and calcein release. Understanding this process is the key to producing more effective immunotoxin sensitizing drugs.
This item is only available in print in the UCF Libraries. If this is your thesis or dissertation, you can help us make it available online for use by researchers around the world by downloading and filling out the Internet Distribution Consent Agreement. You may also contact the project coordinator Kerri Bottorff for more information.
Bachelor of Science (B.S.)
Burnett School of Biomedical Sciences
Molecular Biology and Microbiology
Biomedical Sciences -- Dissertations, Academic;Dissertations, Academic -- Biomedical Sciences
Length of Campus-only Access
Honors in the Major Thesis
Haynes, Elizabeth M., "Mechanism of lipopolyamine-induced immunotozin sensitization in cancer cells" (2010). HIM 1990-2015. 1004.