Vaccination of hormone-refractory prostate cancer patients with peptide cocktail-loaded dendritic cells:: Results of a Phase I clinical trial
Vaccination of hormone-refractory prostate cancer patients with peptide cocktail-loaded dendritic cells:: Results of a Phase I clinical trial
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DOI：
10.1002/pros.20404
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发表时间：
2006-06-01
期刊：
影响因子：
2.8
通讯作者：
Wirth, Manfred P.
中科院分区：
文献类型：
--
作者：
Fuessel, Susanne;Meye, Axel;Wirth, Manfred P.
背景。免疫疗法可能是治疗激素难治性前列腺癌（HRPC）患者的有希望的替代方法。在一项I期临床试验中，我们评估了树突状细胞（DCs）的疫苗接种，该疫苗由五种不同前列腺癌相关抗原（前列腺特异性抗原（PSA）、前列腺特异性膜抗原（PSMA）、survivin、prostein、瞬时受体电位p8 (trp-p8)）衍生的HLAA*0201限制性肽组成。8名HRPC患者每隔一周总共接种4次疫苗。分别采用血清PSA水平测定和酶联免疫斑点（ELISPOT）法监测两组患者的临床和免疫反应。除局部皮肤反应外，未发现任何副作用。1例患者表现出部分缓解（PR； PSA降低50%），另外3例患者表现出稳定的PSA值或减缓的PSA升高。在ELISPOT分析中，4名PSA应答者中有3名也表现出抗原特异性CD8(+) t细胞对prostein、survivin和psma的活化。所描述的方案代表了一个安全可行的概念，以诱导临床和免疫反应。应用从不同抗原衍生的肽鸡尾酒作为一种新的治疗方式，应该允许前列腺癌的遗传和生物学异质性。
BACKGROUND. Immunotherapies might represent promising alternatives for the treatment of patients with hormone-refractory prostate cancer (HRPC). In a Phase I clinical trial, we evaluated a vaccination with dendritic cells (DCs) loaded with a cocktail consisting of HLAA*0201-restricted peptides derived from five different prostate cancer-associated antigens [prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), survivin, prostein, transient receptor potential p8 (trp-p8)].METHODS. Eight HRPC patients received a total of four vaccinations every other week. Clinical and immunological responses were monitored by the determination of the serum PSA levels and by enzyme linked immunospot (ELISPOT) analyses, respectively.RESULTS. Apart from local skin reactions no side effects were noted. One patient displayed a partial response (PR; PSA decrease > 50%) and three other patients showed stable PSA values or decelerated PSA increases. In ELISPOT analyses, three of four PSA responders also showed antigen-specific CD8(+) T-cell activation against prostein, survivin, and PSMA.CONCLUSIONS. The described protocol represents a safe and feasible concept for the induction of clinical and immunological responses. The application of a peptide cocktail-derived from different antigens as a novel treatment modality is supposed to allow for the genetic and biologic heterogeneity of PCa.