Departments of Chemistry and Cancer Biology, The Scripps Research Institute , 130 Scripps Way, Jupiter, Florida 33458, United States.
J Am Chem Soc. 2016 May 18;138(19):6076-94. doi: 10.1021/jacs.6b02954. Epub 2016 May 3.
Methods to monitor and manipulate the immune system are of enormous clinical interest. For example, the development of vaccines represents one of the earliest and greatest accomplishments of the biomedical research enterprise. More recently, drugs capable of "reawakening" the immune system to cancer have generated enormous excitement. But, much remains to be done. All drugs available today that manipulate the immune system cannot distinguish between "good" and "bad" immune responses and thus drive general and systemic immune suppression or activation. Indeed, with the notable exception of vaccines, our ability to monitor and manipulate antigen-specific immune responses is in its infancy. Achieving this finer level of control would be highly desirable. For example, it might allow the pharmacological editing of pathogenic immune responses without restricting the ability of the immune system to defend against infection. On the diagnostic side, a method to comprehensively monitor the circulating, antigen-specific antibody population could provide a treasure trove of clinically useful biomarkers, since many diseases expose the immune system to characteristic molecules that are deemed foreign and elicit the production of antibodies against them. This Perspective will discuss the state-of-the-art of this area with a focus on what we consider seminal opportunities for the chemistry community to contribute to this important field.
监测和操纵免疫系统的方法具有巨大的临床意义。例如，疫苗的开发代表了生物医学研究企业最早和最伟大的成就之一。最近，能够“重新唤醒”免疫系统对抗癌症的药物引起了极大的兴奋。但是，还有很多工作要做。目前所有能够操纵免疫系统的药物都无法区分“好”和“坏”的免疫反应，因此会导致普遍和系统性的免疫抑制或激活。事实上，除了疫苗之外，我们监测和操纵抗原特异性免疫反应的能力还处于起步阶段。实现这种更精细的控制水平将是非常理想的。例如，它可以允许对致病性免疫反应进行药理学编辑，而不会限制免疫系统抵御感染的能力。在诊断方面，一种全面监测循环中抗原特异性抗体群体的方法可以提供丰富的临床有用的生物标志物，因为许多疾病使免疫系统暴露于被认为是外来的特征分子，并引发针对这些分子的抗体产生。本文将讨论该领域的最新技术进展，并重点介绍我们认为化学界有机会为这一重要领域做出贡献的重要机会。
