Interdisciplinary critique of sipuleucel-T as immunotherapy in castration-resistant prostate cancer.
Interdisciplinary critique of sipuleucel-T as immunotherapy in castration-resistant prostate cancer.
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DOI：
10.1093/jnci/djr514
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发表时间：
2012-02-22
期刊：
影响因子：
--
通讯作者：
Iversen P
中科院分区：
文献类型：
--
作者：
Huber ML;Haynes L;Parker C;Iversen P
西普鲁切尔-T于2010年4月29日被美国食品和药物管理局批准为晚期前列腺癌的免疫疗法。为了制造SiPuleucel-T，从患者身上获取的单个核细胞与重组前列腺酸性磷酸酶(PAP)抗原孵育并回输。制造商提出，由PAP外源性激活的抗原提呈细胞可以诱导内源性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已经促使人们呼吁审查试验的设计，在这些试验中，siPuleucel-T显示了4个月的生存益处。此前未发表的siPuleucel-T试验数据显示，在安慰剂组中，年龄较大的患者与年轻患者的总体存活率较差，此前还没有证据表明，这对接受化疗的去势抵抗前列腺癌患者的存活率有预测作用。因为从安慰剂患者身上获得的细胞中有三分之二是冷冻的，而不是从SsiPuleucel-T臂中获得的，所以这种大量重复的细胞损失的有害影响为存活的“好处”提供了一个潜在的替代解释。患者的安全取决于对试验结果的这种可供选择的解释的适当处理。
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 Previously unpublished data from the sipuleucel-T trials show worse overall survival in older vs younger patients in the placebo groups, which have not been shown previously to be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.
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DOI：
10.1186/1742-4933-4-9
发表时间：
2007-12-11
期刊：
Immunity & ageing : I & A
影响因子：
--
作者：
Aspinall, Richard;Del Giudice, Giuseppe;Sambhara, Suryaprakash
通讯作者：
Sambhara, Suryaprakash
DOI：
10.1111/j.1749-6632.2009.05370.x
发表时间：
2010-01-01
期刊：
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影响因子：
--
作者：
Fulop, Tamas;Kotb, Rami;Larbi, Anis
通讯作者：
Larbi, Anis
影响因子：
3.9
作者：
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通讯作者：
Solana, R
影响因子：
11.5
作者：
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通讯作者：
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影响因子：
158.5
作者：
Kantoff, Philip W.;Higano, Celestia S.;Young, J.
通讯作者：
Young, J.