肿瘤免疫抗体药物研发是目前制药工业和药学研究领域最大的研究热点。由于肿瘤的高度异质性/复杂性，单独应用针对单一靶点的肿瘤免疫药物在临床实践中常难以获得预期的治疗效果。联合使用两种（或多种）肿瘤免疫抗体同时靶向调控肿瘤多条信号通路逐步成为肿瘤免疫治疗的关键策略。缺乏准确高效的体内分析方法是制约肿瘤免疫联合用药的主要技术瓶颈。质谱技术的进展为联合治疗策略中多种肿瘤免疫抗体药物同时分析提供了有效的研究平台。本项目在前期工作基础上，建立抗免疫调节因子抗体药物（Pembrolizumab, anti-PD-1）与抗肿瘤细胞表面抗原抗体（anti-CEA mAb 8c2）联合治疗模型，针对肿瘤免疫抗体药物分析中的关键问题，探索和优化以质谱技术为核心同时定量多种肿瘤免疫抗体药物的体内分析方法，对联合用药过程中不同抗体药物体内动力学以及药动学相互作用进行系统研究，为肿瘤免疫联合治疗提供理论基础和数据支持。

Cancer immunotherapies are revolutionizing the field of cancer research and treatment. A plenty of antibody drugs have demonstrated clinical activity across many tumor types as monotherapies. Further advances in the effectiveness of cancer immunotherapies will require targeting antitumor immune response at multiple levels, which may be accomplished through combination approaches. While combinatorial cancer immunotherapy shows great promise in both preclinical models and clinical practices, simultaneous quantification of multiple antibody therapeutics in biological matrices represents a daunting challenge. In this proposal we develop a mass spectrometry based platform that enables high-throughput, streamlined method development for sensitive, selective, and simultaneous quantification of multiple therapeutic antibody in biological samples. This strategy will be applied to the pharmacokinetic investigation of a variety of therapeutic antibody combinations including anti-PD-1/anti-CEA (Pembrolizumab/8c2) in preclinical models. The results are expected to address fundamental pharmacokinetic issues that have not been adequately investigated in previous studies and will provide critical support for the development of effective cancer immunotherapies