Mechanism of lipopolyamine-induced immunotozin sensitization in cancer cells

Abstract

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.

Notes

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Thesis Completion

2010

Semester

Spring

Advisor

Teter, Kenneth

Degree

Bachelor of Science (B.S.)

College

Burnett School of Biomedical Sciences

Degree Program

Molecular Biology and Microbiology

Subjects

Biomedical Sciences -- Dissertations, Academic;Dissertations, Academic -- Biomedical Sciences

Format

Print

Identifier

DP0022508

Language

English

Access Status

Open Access

Length of Campus-only Access

None

Document Type

Honors in the Major Thesis

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