基于高通量肿瘤抗原多肽筛查的常见实体瘤的个体化全疗程精准免疫治疗策略研究

恶性肿瘤是威胁人类健康的重大疾病之一，提高其早期诊断及治疗技术是控制疾病发展、延长患者生命的重要手段。免疫治疗作为突破性肿瘤治疗方法，在一些特定肿瘤患者产生显著疗效的同时，也显示出其治疗的局限性，即出现免疫逃逸。我们前期通过高通量筛选技术建立了针对实体瘤的特异性抗原库，用于早期诊断的同时，能够实现动态监测肿瘤发展各阶段的抗原变化，通过制备多靶点杀伤性T淋巴细胞（MCTL）实施个体化治疗，该技术已获自主知识产权。本研究将以肺癌和结直肠癌为研究对象，大样本验证抗原筛查技术在早期诊断和动态监测的临床准确性，同时建立动物模型深入研究肿瘤免疫逃逸机制，阐明免疫细胞的浸润情况和诱导免疫抑制的关键分子，在此基础上开发MCTL联合治疗方案并通过开展临床研究评估其安全性和有效性。本研究的完成将建立新型肿瘤早期诊断技术，实现对肿瘤抗原的动态实时监测，阐明免疫逃逸机制，调整并优化治疗方案，提高实体肿瘤治疗水平。

Malignant tumors are one of the major diseases that threaten human health. Improving both early diagnosis and treatment techniques are important to control the progression and prolong patient survival. As a breakthrough tumor treatment method, immunotherapy has shown significant therapeutic effects in some tumor patients. However, the limitation was also revealed, that is tumor immune escape. We have established a specific antigen library for solid tumors through high-throughput screening technology. It can be used for early diagnosis and can dynamically monitor antigen changes at various stages of tumor development, therefore, develop personalized treatment for patients through preparation of multi-target cytotoxic T lymphocyte cell (MCTL). We have achieved the intellectual property rights of this technology. In this study, we will further verify the clinical accuracy on early diagnosis and dynamic monitoring in lung cancer and colorectal cancer patients. We will also establish animal models to examine the infiltration of immune cells and explore the immune escape mechanism in the tumor microenvironment. Moreover, we will find the key molecules in immunosuppression, develop new MCTL combination treatment strategies and evaluate its safety and effectiveness by carrying out clinical research. The completion of this study will establish a new type of early diagnosis technology for tumors, implement dynamic real-time monitoring of antigens generated during tumor development, clarify the immune escape mechanism, adjust and optimize treatment programs, and improve the treatment level of solid tumors.