Naked DNA Immunization for Prevention of Prostate Cancer in a Dunning Rat Prostate Tumor Model
Abstract
During year two of the granting period, we continued to study the efficacy of raising cytotoxic human T cell responses against the auto- antigens PAP and PSA with genetically modified autologous dendritic cells, The ability of dendritic cells (DCs), genetically modified with one of two types of plasmid DNA vaccines to stimulate lymphocytes from normal human donors and to generate antigen-specific responses, is compared. The first type, also called "secreted" vaccine (sVac), encode for the full length of the human prostate-specific antigen (PSA) with a signal peptide sequence so that the expressed product is glycosylated and directed to the secretory pathway. The second type, truncated vaccines (tVacs), encode for either HPSA-T or human prostate acidic phosphatase (HPAP-T), both of which lack signal peptide sequences and are retained in the cytosol and degraded by the proteasomes following expression. Additionally, we tested in a rat model the safety of a combination of gene-based vaccines against the human PSMA, PAP and PSA, and their efficacy to prevent tumor development after inoculation with the AT3B-l(exp PSA) cell line. Spleen cells from the immunized rats are cytotoxic to both the parental (AT3B-l) and transfected cell lines. Inoculation of rats with AT3B-l(exp PSA) cells immunize them against human PSA. The immune response could be detected as cytotoxicity against the transfected cell line or as antibodies against the native PSA detected by ELISA.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2004
- Accession Number
- ADA428465
Entities
People
- Milcho S. Mincheff
Organizations
- George Washington University