医学
结直肠癌
免疫系统
癌胚抗原
免疫组织化学
抗原
免疫疗法
接种疫苗
肝切除术
癌症
内科学
肿瘤科
免疫学
胃肠病学
外科
切除术
肿瘤相关抗原
作者
Eyad Elkord,Adam Dangoor,Noel Drury,Richard Harrop,Deborah J. Burt,Jan W. Drijfhout,Caroline Hamer,Danielle Andrews,Stuart Naylor,David Sherlock,Robert E. Hawkins,Peter L. Stern
出处
期刊:Journal of Immunotherapy
[Ovid Technologies (Wolters Kluwer)]
日期:2008-11-01
卷期号:31 (9): 820-829
被引量:48
标识
DOI:10.1097/cji.0b013e3181876ab3
摘要
We investigated the use of a therapeutic vaccine, TroVax in patients undergoing surgical resection of colorectal cancer liver metastases. Systemic immunity generated by vaccination before and after resection of metastases was measured in addition to assessing safety and analyzing the function and phenotype of tumor-associated lymphocytes. Twenty patients were scheduled to receive 2 TroVax vaccinations at 2-week intervals preoperatively and 2 postoperatively; if immune responses were detected, 2 further vaccinations were offered. Blood was taken at trial entry and 2 weeks after each vaccination; tumor biopsies were collected at surgery. 5T4-specific cellular responses were assessed by lymphocyte proliferation and enzyme-linked immunosorbent spot, with antibody responses by enzyme-linked immunosorbent assay. Immunohistochemistry characterized the phenotype of tumor-infiltrating lymphocytes. Seventeen of 19 colorectal cancer patients showed 5T4 expression in the liver metastases or surrounding stroma and 18 mounted a 5T4-specific cellular and/or humoral response. In patients who received at least 4 vaccinations and potentially curative surgery (n=15), those with above median 5T4-specific proliferative responses or T-cell infiltration into the resected tumor showed significantly longer survival compared with those with below median responses. Seven of 8 patients who had preexisting proliferative responses to 5T4 were longer-term survivors; these patients showed significantly higher proliferative responses after vaccination than those who subsequently died. These data suggest that the magnitude of 5T4 proliferative responses and the density of CD3 cells in colorectal cancer liver metastases are associated with longer survival. These observations warrant more studies to identify the precise underlying mechanisms.
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