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

Immunotherapy is a novel treatment for many tumors including prostate cancer. Little is known about the histological changes in prostate biopsies caused by the prostate-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 3 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 posttreatment biopsies were compared. Posttreatment biopsies induced 8 cases with residual adenocarcinoma despite evidences of treatment effect and inflammation, 2 cases did not show any residual tumor, and 1 one case did not have any inflammatory infiltrate or any evidence of treatment effect. The inflammatory infiltrate varied from mild to severe and was composed of mononuclear cells. Greater numbers 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 these morphological changes induced by the PSA-TRICOM will help to interpret the results of future intratumoral vaccine therapy trials. (C) 2018 Published by Elsevier Inc.