Identification of a specific peptide binding to cancer-testis antigen KK-LC-1 from a phage-displayed peptide library
作者单位：The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
会议名称：《2021年中国肿瘤标志物学术大会暨第十五届肿瘤标志物青年科学家论坛》
会议日期：2021年
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
关 键 词：KK-LC-1 Gastric cancer Targeted therapy Phage display Molecular probe
摘 要：Every year there are nearly 1 million new cases of gastric cancer reported worldwide, making it the third leading cause of cancer-related deaths. Diagnosis of gastric cancer mainly depends on the diagnostic radiology examination, which is one of the effective means to predict the metastasis of retroperitoneal lymph nodes in gastric cancer. However, it is not ideal for the diagnosis of metastases less than 0.5 ***-kyushu lung cancer antigen 1(KK-LC-1) is a novel tumor target with great therapeutic potential. The KK-LC-1 antigen was originally found in human lung cancer cells but was soon found to be expressed at high levels in breast cancer and gastric cancer. KK-LC-1 is a type of cancer-testis antigen, which will not be expressed in normal tissues other than testis, placenta, and fetal ovary. Targeting of cancertestis antigen could improve the specificity of anti-tumor drug molecule, which is a unique advantage for targeted *** with strong specificity have many applications in clinical. However, small-molecule peptides have better tumor permeability, better immunogenicity, and pharmacokinetic parameters. A phagedisplay peptide library is comprised of a heterogeneous mixture of billions of phage clones. Through multiple rounds of biological panning for specific antigens, the targeting peptides can be quickly and efficiently *** this study, we screened several candidate peptides from a phage library. Its affinity was confirmed by ELISA and SPR. In cellular immunofluorescence, the targeting peptide showed good tumor cell affinity and could form effective competitive binding with antibodies. Validation in patient tumors and tissue sections also showed excellent specificity. In vivo, the peptides could be effectively enriched in the tumor with little systemic non-specific binding. The enrichment process of target peptides in vivo was reproduced by micro-PET/CT imaging. The radioactivity signal of the nuclide-labeled target peptides at the tumo