Sipuleucel-T: Prototype for Development of Anti-tumor Vaccines
Sipuleucel-T: Prototype for Development of Anti-tumor Vaccines
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DOI：
10.1007/s11912-011-0152-5
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发表时间：
2011-04-01
影响因子：
4.7
通讯作者：
Fishman, Mayer
中科院分区：
文献类型：
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作者：
Carballido, Estrella;Fishman, Mayer
前列腺癌免疫疗法随着最近FDA批准Sipuleucel-T而正式亮相。癌症免疫治疗的新趋势依赖于特定肿瘤相关抗原的鉴定，如前列腺酸性磷酸酶（PAP）。Sipuleucel-T由在体外用重组融合蛋白PA 2024激活的自体树突状细胞组成，PA 2024与粒细胞-巨噬细胞集落刺激因子连接。Sipuleucel-T代表了癌症疫苗开发的原型。临床前和临床数据，以及现有的狭窄的化疗替代和早期免疫治疗试验的里程碑式的研究将进行讨论。关键性试验表明，中位生存期差异为4.1个月，但对无症状或症状轻微的转移性去势抵抗患者的进展时间没有影响。在治疗人群中观察到几种免疫效应，包括对P2024和PAP的抗体和T细胞特异性活性。对于所有新疗法，应评价临床和客观获益与遇到的局限性的程度。本文综述了Sipuleucel-T开发过程中的事件和决策。我们讨论了这种成功的免疫治疗结果如何挑战我们使用它作为一个起点的变化，或试图扩大实际的抗癌进展的抗肿瘤疫苗范例。
Prostate cancer immunotherapy officially debuted with the recent FDA approval of Sipuleucel-T. The novel trend of cancer immunotherapy relies on the identification of particular tumor-associated antigens, like prostatic acid phosphatase (PAP). Sipuleucel-T consists of autologous dendritic cells activated in vitro with recombinant fusion protein PA2024, PAP-linked to granulocyte-macrophage colony-stimulating factor. Sipuleucel-T represents a prototype for the development of cancer vaccines. Preclinical and clinical data as well as landmark studies for the existing narrow chemotherapy alternatives and early immunotherapy trials will be discussed. The pivotal trial demonstrated a 4.1-month difference of median survival, but with no effect on time to progression in asymptomatic or minimally symptomatic metastatic castrate-resistant patients. Several immunologic effects were observed in the treated population, including antibody and T cell-specific activity to P2024 and PAP. With all new therapies the extent of clinical and objective benefits versus encountered limitations should be evaluated. This review highlights the events and decisions in the process of the development of Sipuleucel-T. We discuss how this successful immunotherapy outcome challenges us to use it as a starting point for variations to or try to amplify practical anticancer progress within the antitumor vaccine paradigm.