Affiliations of authors: Dana-Farber Cancer Institute, Boston, MA, USA.
Brigham and Women's Hospital, Boston, MA, USA.
J Natl Cancer Inst. 2022 Feb 7;114(2):310-313. doi: 10.1093/jnci/djab025.
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, which is expressed by prostate cancer cells, potentially leading to lysis of cancer cells. Expanding on 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 cocultured with autologous monocytes pulsed with control or target antigens. Differentially stained effector and target cells were then video recorded during coculture. 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, prostate acid phosphatase, or prostate-specific antigen.
Sipuleucel-T 是一种自体细胞免疫疗法,于 2010 年在美国获批用于治疗转移性去势抵抗性前列腺癌。Sipuleucel-T 治疗可使免疫系统针对前列腺酸性磷酸酶(由前列腺癌细胞表达)进行靶向攻击,从而可能导致癌细胞裂解。在先前报道的 sipuleucel-T 治疗导致细胞杀伤的间接证据基础上,我们试图通过可视化提供细胞裂解的直接证据。我们使用先进的视频技术和 STAMP 试验(NCT01487863)中入组受试者的外周血单个核细胞的可用样本。分离的 CD8+T 细胞用作效应细胞,并与用对照或靶抗原脉冲的自体单核细胞共培养。然后在共培养期间对差异染色的效应细胞和靶细胞进行视频记录。在此,我们展示了来自 sipuleucel-T 治疗受试者的 T 细胞的视频记录和分析,首次直接显示表达前列腺癌靶抗原、前列腺酸性磷酸酶或前列腺特异性抗原的细胞裂解。