Beyond sipuleucel-T: immune approaches to treating prostate cancer.
Beyond sipuleucel-T: immune approaches to treating prostate cancer.
复制标题
超越 sipuleucel-T：治疗前列腺癌的免疫方法。
DOI：
10.1007/s11864-013-0267-z
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发表时间：
2014
影响因子：
4.3
通讯作者：
Fong,Lawrence
中科院分区：
文献类型：
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作者：
Cheng,MichaelL;Fong,Lawrence
目前，sipuleucel-T是唯一被批准的前列腺癌免疫疗法。Sipuleucel-T是一种自体细胞疗法，其针对前列腺酸性磷酸酶（PAP）抗原引发自体抗原呈递细胞。对于无症状或症状轻微的转移性去势抵抗性前列腺癌（CRPC）患者，sipuleucel-T单药治疗是多西他赛治疗前或治疗后的标准治疗选择之一。随着包括阿比特龙和恩扎妥米在内的新治疗方法的批准，这些治疗方法与sipuleucel-T的测序和组合代表了该领域面临的未回答的问题。尽管长期以来一直认为与阿比特龙和化疗联合给药的类固醇具有免疫抑制作用，但早期结果显示，同时使用阿比特龙和泼尼松不会显著影响对该治疗产生免疫应答的能力。需要额外的临床数据来阐明CRPC治疗药物的最佳顺序。目前正在开发几种新型免疫疗法，应考虑纳入临床试验。其中包括PROSTVAC-VF，这是一种编码PSA和T细胞共刺激分子的病毒疫苗，目前正在进行III期临床试验。针对不同抗原（包括PAP）的DNA质粒疫苗也在研究中。ipilimumab是一种针对CTLA-4的单克隆抗体，被批准用于转移性黑色素瘤，也正在评估免疫检查点阻断。尽管这种治疗未能显示多西他赛治疗的CRPC患者的总生存期有显著改善，但在多西他赛治疗前的III期试验结果尚未确定。前列腺癌的常规疗法，如放射和激素疗法，可能具有免疫调节作用。未来的研究领域包括免疫疗法以及其他常规疗法的测序和组合。
Opinion statementAt present, sipuleucel-T represents the only approved immunotherapy for prostate cancer. Sipuleucel-T is an autologous cellular therapy, which primes autologous antigen-presenting cells against the prostatic acid phosphatase (PAP) antigen. For patients with metastatic castrate-resistant prostate cancer (CRPC) who are asymptomatic or minimally symptomatic, sipuleucel-T monotherapy is one of the standard of care treatment options pre- or postdocetaxel. With the approval of new treatments, including abiraterone and enzatutamide, sequencing and combination of these treatments with sipuleucel-T represent unanswered questions facing the field. Whereas steroids that are coadministered with abiraterone and chemotherapy have long been thought to be immunosuppressive, early results show that concurrent abiraterone and prednisone does not significantly impact the ability to develop immune responses to this treatment. Additional clinical data are needed to elucidate optimal sequencing of therapeutic agents in CRPC. Several novel immunotherapies are currently in development, and enrollment in clinical trials should be considered. These include PROSTVAC-VF, a viral vaccine that encodes PSA and T-cell costimulatory molecules, which is currently undergoing phase III clinical trials. DNA plasmid-based vaccines targeting different antigens, including PAP, also are under investigation. Immune checkpoint blockade with ipilimumab, a monoclonal antibody against CTLA-4, which is approved for metastatic melanoma, also is being evaluated. Whereas this treatment failed to show significant improvement in overall survival in CRPC patients treated with docetaxel, results from a phase III trial in the predocetaxel setting are pending. Conventional therapies for prostate cancer, such as radiation and hormonal therapy, may have immunomodulatory effects. Future areas for research include the sequencing and combination of immunotherapies as well as other conventional therapies.