title: An MVA-based vaccine targeting the oncofetal antigen 5T4 in patients undergoing surgical resection of colorectal cancer liver metastases.
abstract: 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.
authors.affiliation: CRUK Immunology, Medical Oncology Groups, Paterson Institute for Cancer Research, University of Manchester, Christie Hospital NHS Trust, Manchester, UK.
authors.forename: Eyad
authors.initials: E
authors.lastname: Elkord
authors.forename: Adam
authors.initials: A
authors.lastname: Dangoor
authors.forename: Noel L
authors.initials: NL
authors.lastname: Drury
authors.forename: Richard
authors.initials: R
authors.lastname: Harrop
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Burt
authors.forename: Jan W
authors.initials: JW
authors.lastname: Drijfhout
authors.forename: Caroline
authors.initials: C
authors.lastname: Hamer
authors.forename: Danielle
authors.initials: D
authors.lastname: Andrews
authors.forename: Stuart
authors.initials: S
authors.lastname: Naylor
authors.forename: David
authors.initials: D
authors.lastname: Sherlock
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hawkins
authors.forename: Peter L
authors.initials: PL
authors.lastname: Stern
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D000368:Aged; D000369:Aged, 80 and over; D000917:Antibody Formation / Q000276:immunology; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines / Q000008:administration & dosage*; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D008113:Liver Neoplasms / Q000401:mortality / Q000556:secondary / Q000601:surgery / Q000628:therapy*; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D019444:Vaccines, DNA
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C504058:TroVax; D019444:Vaccines, DNA; C031192:oncofetal antigens