Kiani-Alikhan, Sorena; (2000) DNA vaccination against human carcinoembryonic antigen; The effect of coding and non-coding sequences. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The immune system has been thought to have the potential to act against tumour cells. On this basis, a variety of strategies have been employed to stimulate antitumour immune responses. This thesis investigates DNA vaccination against human carcinoembryonic antigen (hCEA) as a means of stimulating responses against tumour cells that over express this antigen. DNA vaccination against hCEA in C57BL/6 mice results in weak and unreproducible responses. These responses, however, may be significantly potentiated by fusion of the antigen gene with Tetanus toxoid Fragment-c (Fr-c). Fusion of hCEA gene with a small sequence of oligonucleotides (Tag) may also augment such responses. These response-potentiating sequences may function by coding for helper epitopes or providing immunostimulatory signals (ISS) in their oligonucleotide form. An ISS of 15 base long augmented the antigen presentation ability of murine bone marrow derived dendritic cells. This sequence binds to an intracellular component of CB1 dendritic cells line. Furthermore, this ISS precipitated NF-κB p65 from the cytoplasmic extract of CB1 cells.

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