Pitfalls or promise in prostate cancer immunotherapy - Which is winning?
Pitfalls or promise in prostate cancer immunotherapy - Which is winning?
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DOI：
10.1097/ppo.0b013e318161bffa
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发表时间：
2008-01-01
期刊：
影响因子：
2.2
通讯作者：
Slovin, Susan F.
中科院分区：
文献类型：
--
作者：
Slovin, Susan F.
目的：用疫苗、细胞因子和针对检查点分子的单抗进行免疫治疗已被引入临床领域。尽管所有的方法在临床试验中都证明了对去势转移性前列腺癌患者的安全性，但没有一种方法能够提高总体存活率。设计：I、II和III期试验表明，针对特定的肿瘤相关抗原，免疫耐受可以被消除，但免疫学读数在决定试验能否继续进行方面并不是最优的。结果：组合方法似乎是诱导免疫原性和抗肿瘤效果所必需的。策略包括辐射肿瘤细胞系、共刺激分子或免疫检查点抑制剂，这些都在试验中，并正在严格审查它们对临床终点的影响，如疾病进展和存活时间。讨论：提高疫苗的免疫原性和重新评估如何有效地建立可解释的免疫学终点的策略正在开发中，并似乎成功地影响了这些试验的进展。
Purpose: Immunotherapy with vaccines, cytokines, and monoclonal antibodies against checkpoint molecules has been introduced into the clinical arena. Although all have demonstrated safety in clinical trials in patients with castrate metastatic prostate cancer, no one approach has been able to provide improved overall survival. This article is a review of the current issues and potential resolutions as to how we might go forward in developing and interpreting immunologic trials.Design: Phase I, II, and III trials showed that immunologic tolerance can be abrogated against specific tumor-associated antigens, but the immunologic readouts are suboptimal in determining whether a trial can go forward in its development.Results: Combinatorial approaches appear to be necessary for inducing immunogenicity and antitumor effects. Strategies include irradiated tumor cells lines, costimulatory molecules, or immune checkpoint inhibitors, which are in trials and are under intense scrutiny as to their impact on clinical end points such as time to disease progression and survival.Discussion: Strategies to enhance immunogenicity of vaccines and reassess how to effectively establish interpretable immunologic end points are under development and appear to be successful in affecting how these trials go forward.