基于PD-L1肿瘤非侵入性精准检测的Affibody构建以及体内评价研究

以PD-1/PD-L1抗体为代表的肿瘤免疫治疗作为一种创新的治疗方式已显示出了巨大的优势和发展潜力。但是，PD-1/PD-L1抗体治疗仅对大约20-30%的肿瘤病人有效，而在部分肿瘤中PD-L1阳性的病人治疗的有效率可以大幅度提高。现有的PD-L1检测依赖于肿瘤穿刺活检，而由于PD-L1仅分布在肿瘤部分区域，检测的准确性普遍偏低，亟需研发新的检测策略。我们前期通过PD-L1单链抗体偶联同位素显示可在小鼠模型上对PD-L1阳性肿瘤特异性成像。但是单链抗体分子量还比较大，在体内滞留时间长，偶联的同位素对人体有一定的伤害。Affibody作为高亲和力高稳定性的多肽，代谢较快，在分子检测方面有独特的优势。我们拟构建Affibody筛选平台，筛选能识别PD-L1等跨膜蛋白的多肽小分子，用于肿瘤非侵入性检测，有望代替穿刺活检，提高检测的准确性，为未来筛选临床病人，对病人进行精准治疗奠定理论和实验基础。

Tumor immunotherapy represented by PD-1/PD-L1 antibody has shown great advantages and development potential as an innovative treatment. However, PD-1/PD-L1 antibody treatment is only effective in approximately 20-30% of tumor patients, and the effectiveness of treatment in PD-L1-positive patients in some tumors can be greatly improved. The existing PD-L1 detection relies on tumor biopsy, and since PD-L1 is only distributed in part of the tumor, the accuracy of detection is generally low, and it is urgent to develop a new detection strategy. We have previously demonstrated specific imaging of PD-L1 positive tumors in a mouse model by PD-L1 single-chain antibody-coupled isotopes. However, the molecular weight of the single-chain antibody is relatively large, and the retention time in the body is long, and the coupled isotope has certain damage to the human body. As a high affinity and high stability peptide, Affibody has a fast metabolism and unique advantages in molecular detection. We intend to construct an Affibody screening platform to screen small peptide molecules that recognize transmembrane proteins such as PD-L1, which are used for non-invasive detection of tumors. It is expected to replace biopsy to improve the accuracy of detection, screening clinical patients for patients in the future. Accurate treatment lays the foundation for theory and experimentation.