结直肠CAR-T细胞治疗相关肿瘤靶点的筛选：CEA、EGFR、HER2、Mesothelin、MUC1和EpCAM的表达及共表达状况  

Cancer antigen profiling for colorectal cancer CAR-T therapy: expression and coexpression of CEA,EGFR, HER2, Mesothelin, MUC1 and EpCAM

作　　者：胡阿锦 张畅 龚苗子[1] 王云帆[1] 王跃[1] 王淑芳[1] 张雨 缪琦[1] 崔朝丽 张晋夏[1] HU A-jin;ZHANG Chang;GONG Miao-zi;WANG Yun-fan;WANG Yue;WANG Shu-fang;ZHANG Yu;MIAO Qi;CUI Zhao-li;ZHANG Jin-xia(Department of Pathology,Shougang Hospital,Peking University,Beijing 100144,China)

机构地区：[1]北京大学首钢医院病理科

出　　处：《消化肿瘤杂志（电子版）》2019年第3期225-230,共6页Journal of Digestive Oncology(Electronic Version)

摘　　要：目的分析CEA、EGFR等肿瘤相关抗原作为CAR-T治疗靶点在结直肠癌中的分布。方法回顾并选取2014年-2017年的122例结直肠癌病例,应用免疫组织化学法检测肿瘤相关抗原CEA、EGFR、HER2、Mesothelin、MUC1和EpCAM在结直肠癌组织中蛋白表达范围和强度。结果除HER2(37.5%)外,其它肿瘤相关抗原在结直肠癌中表达阳性率均在50%以上,EpCAM(100%)、CEA(99.1%)、EGFR(96%)、Mesothelin(67.9%)、MUC1(67%)。CEA(94.6%)和EpCAM(100%)强表达的比例较高,EGFR和Mesothelin分别在10.7%和31.2%的病例中强表达,HER2和MUC1均未见强表达病例。EpCAM(99.1%)、CEA(98.2%)、EGFR(56.2%)在结直肠癌中的表达范围较广(大于50%的肿瘤细胞表达),Mesothelin和MUC1均灶状表达。除EpCAM外,其它肿瘤相关抗原特异性均较好。仅28.6%的病例共表达CEA/EGFR/HER2/Mesothelin。64.3%的病例共表达CEA/EGFR/Mesothelin。其余三抗原共表达的病例均少于50%。高达95.5%的结直肠癌病例共表达CEA/EGFR。除CEA/Mesothelin(67%)及Mesothelin/HER2(65.2%)外,其余两抗原共表达的病例均少于50%。结论肿瘤相关抗原CEA和EGFR可作为结直肠癌CAR-T治疗多靶点组合方案的选择。Objective To develop cancer antigen-targeted CAR-T therapeutic strategies for colorectal cancer,we investigated the individual and coexpressions of the tumor-associated antigens CEA,EGFR,HER2,Mesothelin,MUC1 and EpCAM in colorectal cancer.Methods All available hematoxylin and eosin-stained slides from patients who were diagnosed with colorectal cancer(2014-2017)were reviewed.Intensity and distribution for each antigen were assessed by immunohistochemistry in 122 of colorectal cancer cases.Results Positive expression of EpCAM,CEA,EGFR,Mesothelin,MUC1 and HER2 were demonstrated in 100%,99.1%,96%,67.9%,67%and 37.5%of colorectal cancer cases,respectively.Strong expression of CEA,EpCAM,EGFR and Mesothelin were found in 94.6%,100%,10.7%and 31.2%of colorectal cancer cases,while neither HER2 nor MUC1 was strong expression.Distribution≥50%of EpCAM,CEA and EGFR positive tumor cells were observed in 99.1%,98.2%and 56.2%of colorectal cancer cases,respectively,while both mesothelin and MUC1 were multifocal express in all of colorectal cancer.In addition to EpCAM,specificity of all the other tumor-associated antigens was much better.CEA/EGFR/HER2/Mesothelin was coexpressed in only 28.6%of colorectal cancer cases.Coexpression of CEA/EGFR/Mesothelin was demonstrated in 64.3%of colorectal cancer cases.All the other triple antigen coexpression was demonstrated in less than 50%of colorectal cancer cases.CEA/EGFR were coexpressed in 95.5%of colorectal cancer cases.Except CEA/Mesothelin(67%)and Mesothelin/HER2(65.2%),the other double antigen coexpression was demonstrated in less than 50%of colorectal cancer cases.Conclusions Tumorr-associated antigens CEA and EGFR can be choose for developing multi-targeted CAR-T therapeutic strategies for colorectal cancer patients.

关 键 词：结直肠癌 CAR-T 肿瘤相关抗原 免疫组织化学法 

分 类 号：R73[医药卫生—肿瘤]