Merck & Co., Inc., Palo Alto, California, USA.
AAPS J. 2018 Apr 27;20(4):66. doi: 10.1208/s12248-018-0229-2.
With the recent advances in cancer immunotherapy, it is now evident that the antigen-specific activation of the patients' immune responses can be utilized for achieving significant therapeutic benefits. Novel molecules have been developed and promising advances have been achieved in cancer therapy. The recent success of cancer immunotherapy clearly reflects the novelty of the approach and importance of this class of therapeutics. Due to the nature of immunotherapy, i.e., harnessing the patient's immune system, it becomes critical to evaluate the important variables that can guide preclinical development, translational strategies, patient selection, and effective clinical dosing paradigms following single and combination therapies. To further boost the durability and efficacy profiles of IO (immuno-oncology) drugs following single agent therapy, novel combination therapies are being sought. Combination strategies have become critical for enhancing the anti-tumor immunity in broader cancer indications. Comprehensive methods are being developed to quantify the synergistic combination effect profiles at various development phases. Further evaluation of the signaling and pathway components can potentially establish a unique "signature" characteristic for specific combination therapies following modulation of various immunomodulatory pathways. In this article, critical topics related to preclinical, translational, and clinical development of IO agents are discussed.
随着癌症免疫疗法的最新进展，现在很明显，患者免疫反应的抗原特异性激活可以用于实现显著的治疗益处。已经开发出了新的分子，并在癌症治疗方面取得了有希望的进展。癌症免疫疗法的最近成功清楚地反映了该方法的新颖性和这类治疗的重要性。由于免疫疗法的性质，即利用患者的免疫系统，评估可以指导临床前开发、转化策略、患者选择以及单药和联合治疗后有效临床给药方案的重要变量变得至关重要。为了进一步提高单药治疗后 IO（免疫肿瘤学）药物的持久性和疗效，正在寻求新的联合治疗方案。联合治疗策略对于增强更广泛的癌症适应证中的抗肿瘤免疫至关重要。正在开发综合方法来量化各个开发阶段的协同组合效应谱。对信号和途径成分的进一步评估有可能为特定免疫调节途径的各种调节后建立独特的“特征”。本文讨论了 IO 药物的临床前、转化和临床开发的关键主题。
