Videos of Sipuleucel-T Programmed T Cells Lysing Cells That Express Prostate Cancer Target Antigens.

Abstract

Sipuleucel-T, an autologous cellular immunotherapy, was approved to treat metastatic castration-resistant prostate cancer in 2010 in the United States. Treatment with sipuleucel-T primes the immune system to target prostate acid phosphatase (PAP), which is expressed by prostate cancer cells, potentially leading to lysis of cancer cell. Expanding upon previously reported indirect evidence of cell killing with sipuleucel-T treatment, we sought to provide direct evidence of cell lysis through visualization. We used advanced video technology and available samples of peripheral blood mononuclear cells from subjects enrolled in the STAMP trial (NCT01487863). Isolated CD8+ T cells were used as effector cells and co-cultured with autologous monocytes pulsed with control or target antigens. Differentially stained effector and target cells were then video-recorded during co-culture. Here, we present video recordings and analyses of T cells from sipuleucel-T-treated subjects showing-for the first time-direct lysis of cells that express prostate cancer target antigens, PAP or prostate-specific antigen.