Maciejko Laura, Smalley Munisha, Goldman Aaron
Integrative Immuno-Oncology Center, Mitra Biotech Woburn, MA 01801, USA.
Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
J Mol Biomark Diagn. 2017 Sep;8(5). doi: 10.4172/2155-9929.1000350. Epub 2017 Jun 28.
The vision and strategy for the 21st century treatment of cancer calls for a personalized approach in which therapy selection is designed for each individual patient. While genomics has led the field of personalized cancer medicine over the past several decades by connecting patient-specific DNA mutations with kinase-targeted drugs, the recent discovery that tumors evade immune surveillance has created unique challenges to personalize cancer immunotherapy. In this mini-review we will discuss how personalized medicine has evolved recently to accommodate the emerging era of cancer immunotherapy. Moreover, we will discuss novel platform technologies that have been engineered to address some of the persisting limitations.
Beginning with early evidence in personalized medicine, we discuss how biomarker-driven approaches to predict clinical success have evolved to account for the heterogeneous tumor ecosystem. In the emerging field of cancer immunotherapy, this challenge requires the use of a novel set of tools, distinct from the classic approach of next-generation genomic sequencing-based strategies. We will introduce new techniques that seek to tailor immunotherapy by re-programming patient-autologous T-cells, and new technologies that are emerging to predict clinical efficacy by mapping infiltration of lymphocytes, and harnessing fully humanized platforms that reconstruct and interrogate immune checkpoint blockade, .
While cancer immunotherapy is now leading to durable outcomes in difficult-to-treat cancers, success is highly variable. Developing novel approaches to study cancer immunotherapy, personalize treatment to each patient, and achieve greater outcomes is penultimate to developing sustainable cures in the future. Numerous techniques are now emerging to help guide treatment decisions, which go beyond simple biomarker-driven strategies, and are now we are seeking to interrogate the entirety of the dynamic tumor ecosystem.
综述目的:21世纪癌症治疗的愿景和策略要求采用个性化方法,即针对每个患者设计治疗方案。在过去几十年里,基因组学通过将患者特异性DNA突变与激酶靶向药物联系起来,引领了个性化癌症医学领域。然而,最近发现肿瘤会逃避免疫监视,这给个性化癌症免疫治疗带来了独特挑战。在这篇小型综述中,我们将讨论个性化医学最近如何发展以适应癌症免疫治疗的新时代。此外,我们还将讨论为解决一些持续存在的局限性而设计的新型平台技术。
最新发现:从个性化医学的早期证据开始,我们讨论了基于生物标志物预测临床成功的方法如何发展以适应异质性肿瘤生态系统。在新兴的癌症免疫治疗领域,这一挑战需要使用一套与基于下一代基因组测序的经典策略不同的新工具。我们将介绍通过对患者自体T细胞进行重新编程来定制免疫治疗的新技术,以及通过绘制淋巴细胞浸润情况来预测临床疗效的新技术,还有利用完全人源化平台来重建和研究免疫检查点阻断的新技术。
总结:虽然癌症免疫治疗目前在难治性癌症中取得了持久疗效,但疗效差异很大。开发研究癌症免疫治疗的新方法、为每个患者个性化治疗并取得更好的疗效,对于未来开发可持续的治愈方法至关重要。现在有许多技术正在涌现,以帮助指导治疗决策,这些技术超越了简单的基于生物标志物的策略,我们现在正试图研究整个动态肿瘤生态系统。