Date of Award

2006

Degree Type

Thesis

Degree Name

Master of Science

Program

Microbiology and Immunology

Supervisor

Dr. John McCormick

Abstract

It has been demonstrated that tumour reactive cytotoxic T lymphocytes (CTLs) are capable of employing a potent effector mechanism against malignant cells. However, the frequency of these CTLs is too low to interfere with the proliferation of malignant cells. The use of a bacterial superantigen (SAg) to activate large numbers of CTLs may effectively eliminate tumour cells. Specificity of this toxin for a particular tumor cell type can be generated through the fusion of a SAg with an antibody to create an immunotoxin which recognizes a tumour specific antigen. This work describes the development of novel antibody-SAg fusions between SpeC and a single-chain variable fragment (scFv) antibody that recognizes the 5T4 oncofetal antigen. We have demonstrated that these fusion proteins maintain SAg function and specifically bind to HEK 293 cells which we have engineered to express the 5T4 antigen. Future experiments using these reagents will address the efficacy of these immunotoxins in appropriate animal models of colorectal cancer (CRC)

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