An MVA-based vaccine targeting the oncofetal antigen 5T4 in patients undergoing surgical resection of colorectal cancer liver metastases.

Eyad Elkord, Adam Dangoor, Noel L. Drury, Richard Harrop, Deborah J. Burt, Jan W. Drijfhout, Caroline Hamer, Danielle Andrews, Stuart Naylor, David Sherlock, Robert E. Hawkins, Peter L. Stern

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)820-829
Number of pages10
JournalJournal of immunotherapy (Hagerstown, Md. : 1997)
Volume31
Issue number9
Publication statusPublished - Nov 2008
Externally publishedYes

Fingerprint

Liver Neoplasms
Colorectal Neoplasms
Vaccination
Neoplasm Metastasis
Lymphocytes
Phenotype
Tumor-Infiltrating Lymphocytes
Neoplasms
Immunosorbents
Survival
Therapeutic Uses
Antibody Formation
Survivors
oncofetal antigens
MVA vaccine
Immunity
Vaccines
Cell Count
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

Cite this

An MVA-based vaccine targeting the oncofetal antigen 5T4 in patients undergoing surgical resection of colorectal cancer liver metastases. / Elkord, Eyad; Dangoor, Adam; Drury, Noel L.; Harrop, Richard; Burt, Deborah J.; Drijfhout, Jan W.; Hamer, Caroline; Andrews, Danielle; Naylor, Stuart; Sherlock, David; Hawkins, Robert E.; Stern, Peter L.

In: Journal of immunotherapy (Hagerstown, Md. : 1997), Vol. 31, No. 9, 11.2008, p. 820-829.

Research output: Contribution to journalArticle

Elkord, E, Dangoor, A, Drury, NL, Harrop, R, Burt, DJ, Drijfhout, JW, Hamer, C, Andrews, D, Naylor, S, Sherlock, D, Hawkins, RE & Stern, PL 2008, 'An MVA-based vaccine targeting the oncofetal antigen 5T4 in patients undergoing surgical resection of colorectal cancer liver metastases.', Journal of immunotherapy (Hagerstown, Md. : 1997), vol. 31, no. 9, pp. 820-829.
Elkord, Eyad ; Dangoor, Adam ; Drury, Noel L. ; Harrop, Richard ; Burt, Deborah J. ; Drijfhout, Jan W. ; Hamer, Caroline ; Andrews, Danielle ; Naylor, Stuart ; Sherlock, David ; Hawkins, Robert E. ; Stern, Peter L. / An MVA-based vaccine targeting the oncofetal antigen 5T4 in patients undergoing surgical resection of colorectal cancer liver metastases. In: Journal of immunotherapy (Hagerstown, Md. : 1997). 2008 ; Vol. 31, No. 9. pp. 820-829.
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