Identification of Prostate Specific Antigens for Immunotherapy Vaccines

摘要

The limiting step in the development of antigen specific vaccines for the immunotherapy of cancer is the identification of tissue or cancer specific antigens capable of activating a strong immune response. Many antigens with the desired specificity have been identified but their function as target antigens in immunotherapy are unknown. For prostate cancer several antigens with a prostate restricted expression pattern, including prostate specific antigen (PSA), prostate specific membrane antigen (PSMA), prostatic acid phosphatase (PAP), and human kallikrein 2 (hK2), are available for immunotherapy studies; however, their ability to induce strong T cell responses to date has not been demonstrated. The work outlined in this proposal is designed to identify biologically relevant, immunodominant antigens that have prostate restricted expression. The hypothesis is that transgenic mice expressing the human A2. 1 major histocompatibility antigen, the most commonly expressed class I MHC molecule, can be used to screen for immunodominant antigens in vivo from cDNA libraries enriched for prostate cancer genes. The antigen discovery process utilizes known technology in a novel way to streamline the process of identifying immunologically important antigens. Although novel applications of technology are outlined as the primary approach to antigen identification, established alternatives are described to assure the technical success of the project. To accomplish the task of antigen identification, cDNA libraries enriched for expressed prostate tissue genes were developed and formal demonstration of the ability to use mRNA-pulsed dendritic cells as antigen presenting cells to immunize the transgenic A2. 1 mice has been completed.