Morphological changes induced by intraprostatic PSA-based vaccine in prostate cancer biopsies (phase I clinical trial)

Summary Immunotherapy is a novel treatment for many tumors including prostate cancer. Little is known about the histological changes in prostate biopsies caused by the prostatic-specific antigen (PSA)-based vaccine. This study evaluated the histopathological effects in prostate biopsies of recombinant fowlpox (rF) virus-based vaccine engineered to present the PSA and three costimulatory molecules (collectively labeled as PSA-TRICOM). This vaccine has shown that it can break tolerance of the PSA, and its administration directly into a tumor enables the affected tumor cells to act as antigen-presenting cells activating new T-cells, and broadening the immune response to recognize and kill tumor. We studied 10 patients with recurrent prostate cancer who had failed radiation therapy and/or androgen-deprivation therapy. Pre- and post-treatment biopsies were compared. Post-treatment biopsies induced 8 cases with residual adenocarcinoma despite evidences treatment effect and inflammation, two cases did not show any residual tumor; and only one case did not have any inflammatory infiltrate or any evidenced treatment effect. The inflammatory infiltrate varied from mild to severe, and was composed of mononuclear cells. Greater numbers amount of infiltrating CD8+ lymphocytes were identified around prostatic glands and within the epithelial lining. The most remarkable feature was the presence of increased eosinophils around the glands and stroma. Three cases showed areas of necrosis surrounded by lymphocytes and palisading epithelioid macrophages arranged in granuloma-like pattern with multinucleated giant cells. This description of l these morphological changes induced by the PSA-TRICOM will help to interpret the results of future intratumoral vaccine therapy trials.