Sipuleucel-T (Provenge) autologous vaccine approved for treatment of men with asymptomatic or minimally symptomatic castrate-resistant metastatic prostate cancer
Sipuleucel-T (Provenge) autologous vaccine approved for treatment of men with asymptomatic or minimally symptomatic castrate-resistant metastatic prostate cancer
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DOI：
10.4161/hv.19795
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发表时间：
2012-04-01
影响因子：
4.8
通讯作者：
Hahn, Noah M.
中科院分区：
文献类型：
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作者：
Gardner, Thomas A.;Elzey, Bennett D.;Hahn, Noah M.
SiPuleucel-T(Provenge)(sip-T)是一种一流的治疗性自体疫苗，被批准用于治疗无症状或最小症状的去势耐药转移性前列腺癌。该产品是数十年的基础免疫学和前列腺癌研究以及13年的临床试验研究的成果。SIP-T代表了癌症治疗的范式转变，并代表了第一个被批准的自体治疗性癌症疫苗，它已经证明了生存的好处。该产品的潜在好处是极高的风险收益比，这将允许将该方法与其他毒性更高的疗法相结合。有利的受益风险也将为在疾病状态早期研究该产品并与当地疗法相结合的试验提供机会。能够针对更局部或更低体积的疾病将在更长的时间内最大限度地发挥治疗效益。这种方法平台的新颖性可以用于治疗任何具有肿瘤特异性细胞表面靶点的癌症。Sip-T的主要产品是患者在体外暴露于人GM-CSF和PAP的嵌合蛋白后，从白细胞分离中重新输注抗原提呈细胞。在转移性CRPC患者中，在一个月内输注这些激活细胞三次，中位生存期显著增加4.1mo，死亡风险降低22.5%。这种重新注入激活的免疫细胞的主要副作用是一种类似流感的综合征，包括寒战、疲劳、发烧、背痛、恶心、关节疼痛和头痛，频率从高到低。临床试验期间的免疫监测也显示了特定的细胞和抗体免疫反应，表明PAP过继免疫治疗的机制是这种生存益处的背后。该产品还可以作为针对其他癌症的靶向免疫治疗的原则证明，这些癌症具有明确的细胞表面标记。总而言之，基于生存益处和非常可耐受的安全性而批准的sip-T将(1)增强我们护理晚期前列腺癌男性的能力，(2)允许进一步研究这种方法，并与具有不同作用机制和非重叠毒性的其他疗法相结合，(3)允许在疾病进程的早期进行进一步研究。
Sipuleucel-T (Provenge) (Sip-T) is first-in class as a therapeutic autologous vaccine approved for the treatment of men with asymptomatic or minimally symptomatic castrate-resistant metastatic prostate cancer. This product is the culmination of decades of basic immunological and prostate cancer investigations and 13 years of clinical trial investigations. Sip-T represents a paradigm shift in cancer therapeutics and represents the first approved autologous therapeutic cancer vaccine, which has demonstrated a survival benefit. The potential benefit of this product is the excellent risk to benefit ratio, which will allow for the combination of this approach with other more toxic therapies. The favorable risk to benefit will also afford the opportunity for trials investigating this product earlier in the disease state and in combination with local therapies. The ability to target more localized or lower volume disease will maximize the therapeutic benefit over a longer period of time. The novelty of the platform of this approach could be used to treat any cancer with a tumor-specific cell surface target. The main product of Sip-T is the re-infusion of a patient's antigen presenting cells from leukapheresis after ex-vivo exposure to a chimeric protein of human GM-CSF and PAP. In metastatic CRPC patients, three infusions of these activated cells over a month lead to statistically significant 4.1 mo increase in median survival and a 22.5% reduction in risk of death. The main side effect from this re-infusion of activated immune cells is a "flu-like" syndrome that includes chills, fatigue, fevers, back pain, nausea, joints aches and headaches in decreasing order of frequency. Immune monitoring during the clinical trials also demonstrated a specific cellular and antibody immune response, suggesting the proposed mechanism of adoptive immunotherapy to PAP was behind this survival benefit. This product also serves as a proof of principle for targeted immunotherapy for others cancers with defined cell surface markers. In summary, the approval of Sip-T based on a survival benefit and very tolerable safety profile will (1) enhance our ability to care for men with advanced prostate cancer, (2) allow for further investigations of this approach in combination with others therapies with different mechanisms of action and non-overlapping toxicities and (3) allow further investigations earlier in the course of the disease.