J Natl Cancer Inst. 2012 Feb 22;104(4):273-9. doi: 10.1093/jnci/djr514. Epub 2012 Jan 9.
Sipuleucel-T was approved by the US Food and Drug Administration on April 29, 2010, as an immunotherapy for late-stage prostate cancer. To manufacture sipuleucel-T, mononuclear cells harvested from the patient are incubated with a recombinant prostatic acid phosphatase (PAP) antigen and reinfused. The manufacturer proposes that antigen-presenting cells exogenously activated by PAP induce endogenous T-cells to attack PAP-bearing prostate cancer cells. However, the lack of demonstrable tumor responses has prompted calls for scrutiny of the design of the trials in which sipuleucel-T demonstrated a 4-month survival benefit. Previously unpublished data from the sipuleucel-T trials show worse overall survival in older vs younger patients in the placebo groups, which have not been shown previously to be prognostic for survival in castration-resistant prostate cancer patients receiving chemotherapy. Because two-thirds of the cells harvested from placebo patients, but not from the sipuleucel-T arm, were frozen and not reinfused, a detrimental effect of this large repeated cell loss provides a potential alternative explanation for the survival "benefit." Patient safety depends on adequately addressing this alternative explanation for the trial results.
Sipuleucel-T 于 2010 年 4 月 29 日获得美国食品和药物管理局批准，作为晚期前列腺癌的免疫疗法。为了制造 sipuleucel-T，从患者身上采集的单核细胞与重组前列腺酸性磷酸酶（PAP）抗原孵育后再输注回体内。制造商提出，PAP 体外激活的抗原呈递细胞诱导内源性 T 细胞攻击携带 PAP 的前列腺癌细胞。然而，缺乏可证明的肿瘤反应促使人们对 sipuleucel-T 显示出 4 个月生存获益的试验设计进行审查。来自 sipuleucel-T 试验的先前未公布的数据显示，安慰剂组中年龄较大的患者的总体生存率比年龄较小的患者差，而此前在接受化疗的去势抵抗性前列腺癌患者中，这一指标并未显示与生存预后相关。由于从安慰剂组患者身上采集的三分之二的细胞被冷冻而未再输注，而 sipuleucel-T 组没有这种情况，这种大量反复的细胞丢失可能会产生负面影响，为生存“获益”提供了一种潜在的替代解释。患者安全取决于充分解决试验结果的这一替代解释。
