Naked DNA Immunization of Prevention of Prostate Cancer in a Dunning Rat Prostate Tumor Model
Final rept. 1 Jun 2002-31 May 2006
GEORGE WASHINGTON UNIV WASHINGTON DC
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After cloning a truncated no peptide leader sequence versions of the human prostate acid phosphatase H-PAP-T, the human prostate-specific antigen HPSA- T and the rat analogue of the human PSMA R- PSMA -S, all plasmids were produced under GLP conditions. Their safety was tested in rats and the efficacy to stimulate T cells and to prevent development of transplantable tumors was shown in a rat model. Best protection was obtained following immunization with a cocktail containing all plasmids and a plasmid encoding rat GM-CSF. None of the animals immunized with the truncated plasmids developed antibodies against the native antigen while immunization with a plasmid encoding for an antigen that was secreted did. The antibodies were of mixed Th1 and Th2 type IgG1 and IgG2a. When priming was performed with the truncated version of the vaccines HPSMA-T or HPSA-T, however and boosting with the secreted ones, the antibodies were mainly of the Th1 complement-binding type IgG2a and IgG2b. The best protection was achieved when priming was performed with a plasmid encoding a xenogeneic protein and boosting with a plasmid encoding a syngeneic one. Genetic modification of rat tumor cells that led to expression of human xeno antigens, made them immunogenic, identifying other possible practical applications for vaccine design.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research