Immune evasion mechanisms in colorectal cancer liver metastasis patients vaccinated with TroVax (MVA-5T4)

Eyad Elkord, Adam Dangoor, Deborah J. Burt, Thomas D. Southgate, Sai Daayana, Richard Harrop, Jan W. Drijfhout, David Sherlock, Robert E. Hawkins, Peter L. Stern

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

We have recently reported the results of a phase II trial in which two TroVax [modified vaccinia ankara (MVA) encoding the tumour antigen 5T4] vaccinations were given to patients both pre- and post-surgical resection of liver metastases secondary to colorectal cancer (CRC). 5T4-specific cellular responses were assessed at the entry and 2 weeks after each vaccination by proliferation of fresh lymphocytes and ELISA for antibody responses; 18 from the 19 CRC patients mounted a 5T4-specific cellular and/or humoral response. Here, we present a comparison of individual and between patient responses over the course of the treatments using cryopreserved peripheral blood mononuclear cells (PBMC) samples from the baseline until after the fourth vaccination at 14 weeks. Assays used were proliferation assay with 5T4-Fc fusion protein, overlapping 32mer 5T4 peptides, MVA-LacZ and MVA-5T4 infected autologous monocytes. Responses to 5T4 protein or one or more peptide pools were pre-existing in 12/20 patients and subsequently 10 and 12 patients showed boosted and/or de novo responses, respectively. Cumulatively, 13/20 patients showed proliferative responses by week 14. We also assessed the levels of systemic T regulatory cells, plasma cytokine levels, phenotype of tumour-infiltrating lymphocytes including T regulatory cells and tumour HLA class I loss of expression. More than half of the patients showed phenotypes consistent with relative immune suppression and/or escape highlighting the complexity of positive and negative factors challenging any simple correlation with clinical outcome.

Original languageEnglish
Pages (from-to)1657-1667
Number of pages11
JournalCancer Immunology, Immunotherapy
Volume58
Issue number10
DOIs
Publication statusPublished - Oct 2009
Externally publishedYes

Fingerprint

Immune Evasion
Vaccinia
Liver Neoplasms
Colorectal Neoplasms
Neoplasm Metastasis
Vaccination
Regulatory T-Lymphocytes
Phenotype
Tumor-Infiltrating Lymphocytes
Peptides
Neoplasm Antigens
TroVax
Antibody Formation
Monocytes
Blood Cells
Proteins
Enzyme-Linked Immunosorbent Assay
Lymphocytes
Cytokines
Liver

Keywords

  • 5T4
  • Colorecta cancer
  • Immune evasion
  • T regulatory cell
  • TroVax

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Immunology
  • Immunology and Allergy
  • Medicine(all)

Cite this

Immune evasion mechanisms in colorectal cancer liver metastasis patients vaccinated with TroVax (MVA-5T4). / Elkord, Eyad; Dangoor, Adam; Burt, Deborah J.; Southgate, Thomas D.; Daayana, Sai; Harrop, Richard; Drijfhout, Jan W.; Sherlock, David; Hawkins, Robert E.; Stern, Peter L.

In: Cancer Immunology, Immunotherapy, Vol. 58, No. 10, 10.2009, p. 1657-1667.

Research output: Contribution to journalArticle

Elkord, E, Dangoor, A, Burt, DJ, Southgate, TD, Daayana, S, Harrop, R, Drijfhout, JW, Sherlock, D, Hawkins, RE & Stern, PL 2009, 'Immune evasion mechanisms in colorectal cancer liver metastasis patients vaccinated with TroVax (MVA-5T4)', Cancer Immunology, Immunotherapy, vol. 58, no. 10, pp. 1657-1667. https://doi.org/10.1007/s00262-009-0674-y
Elkord, Eyad ; Dangoor, Adam ; Burt, Deborah J. ; Southgate, Thomas D. ; Daayana, Sai ; Harrop, Richard ; Drijfhout, Jan W. ; Sherlock, David ; Hawkins, Robert E. ; Stern, Peter L. / Immune evasion mechanisms in colorectal cancer liver metastasis patients vaccinated with TroVax (MVA-5T4). In: Cancer Immunology, Immunotherapy. 2009 ; Vol. 58, No. 10. pp. 1657-1667.
@article{c80d55956a594961b413f7048b16de90,
title = "Immune evasion mechanisms in colorectal cancer liver metastasis patients vaccinated with TroVax (MVA-5T4)",
abstract = "We have recently reported the results of a phase II trial in which two TroVax [modified vaccinia ankara (MVA) encoding the tumour antigen 5T4] vaccinations were given to patients both pre- and post-surgical resection of liver metastases secondary to colorectal cancer (CRC). 5T4-specific cellular responses were assessed at the entry and 2 weeks after each vaccination by proliferation of fresh lymphocytes and ELISA for antibody responses; 18 from the 19 CRC patients mounted a 5T4-specific cellular and/or humoral response. Here, we present a comparison of individual and between patient responses over the course of the treatments using cryopreserved peripheral blood mononuclear cells (PBMC) samples from the baseline until after the fourth vaccination at 14 weeks. Assays used were proliferation assay with 5T4-Fc fusion protein, overlapping 32mer 5T4 peptides, MVA-LacZ and MVA-5T4 infected autologous monocytes. Responses to 5T4 protein or one or more peptide pools were pre-existing in 12/20 patients and subsequently 10 and 12 patients showed boosted and/or de novo responses, respectively. Cumulatively, 13/20 patients showed proliferative responses by week 14. We also assessed the levels of systemic T regulatory cells, plasma cytokine levels, phenotype of tumour-infiltrating lymphocytes including T regulatory cells and tumour HLA class I loss of expression. More than half of the patients showed phenotypes consistent with relative immune suppression and/or escape highlighting the complexity of positive and negative factors challenging any simple correlation with clinical outcome.",
keywords = "5T4, Colorecta cancer, Immune evasion, T regulatory cell, TroVax",
author = "Eyad Elkord and Adam Dangoor and Burt, {Deborah J.} and Southgate, {Thomas D.} and Sai Daayana and Richard Harrop and Drijfhout, {Jan W.} and David Sherlock and Hawkins, {Robert E.} and Stern, {Peter L.}",
year = "2009",
month = "10",
doi = "10.1007/s00262-009-0674-y",
language = "English",
volume = "58",
pages = "1657--1667",
journal = "Cancer Immunology and Immunotherapy",
issn = "0340-7004",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "10",

}

TY - JOUR

T1 - Immune evasion mechanisms in colorectal cancer liver metastasis patients vaccinated with TroVax (MVA-5T4)

AU - Elkord, Eyad

AU - Dangoor, Adam

AU - Burt, Deborah J.

AU - Southgate, Thomas D.

AU - Daayana, Sai

AU - Harrop, Richard

AU - Drijfhout, Jan W.

AU - Sherlock, David

AU - Hawkins, Robert E.

AU - Stern, Peter L.

PY - 2009/10

Y1 - 2009/10

N2 - We have recently reported the results of a phase II trial in which two TroVax [modified vaccinia ankara (MVA) encoding the tumour antigen 5T4] vaccinations were given to patients both pre- and post-surgical resection of liver metastases secondary to colorectal cancer (CRC). 5T4-specific cellular responses were assessed at the entry and 2 weeks after each vaccination by proliferation of fresh lymphocytes and ELISA for antibody responses; 18 from the 19 CRC patients mounted a 5T4-specific cellular and/or humoral response. Here, we present a comparison of individual and between patient responses over the course of the treatments using cryopreserved peripheral blood mononuclear cells (PBMC) samples from the baseline until after the fourth vaccination at 14 weeks. Assays used were proliferation assay with 5T4-Fc fusion protein, overlapping 32mer 5T4 peptides, MVA-LacZ and MVA-5T4 infected autologous monocytes. Responses to 5T4 protein or one or more peptide pools were pre-existing in 12/20 patients and subsequently 10 and 12 patients showed boosted and/or de novo responses, respectively. Cumulatively, 13/20 patients showed proliferative responses by week 14. We also assessed the levels of systemic T regulatory cells, plasma cytokine levels, phenotype of tumour-infiltrating lymphocytes including T regulatory cells and tumour HLA class I loss of expression. More than half of the patients showed phenotypes consistent with relative immune suppression and/or escape highlighting the complexity of positive and negative factors challenging any simple correlation with clinical outcome.

AB - We have recently reported the results of a phase II trial in which two TroVax [modified vaccinia ankara (MVA) encoding the tumour antigen 5T4] vaccinations were given to patients both pre- and post-surgical resection of liver metastases secondary to colorectal cancer (CRC). 5T4-specific cellular responses were assessed at the entry and 2 weeks after each vaccination by proliferation of fresh lymphocytes and ELISA for antibody responses; 18 from the 19 CRC patients mounted a 5T4-specific cellular and/or humoral response. Here, we present a comparison of individual and between patient responses over the course of the treatments using cryopreserved peripheral blood mononuclear cells (PBMC) samples from the baseline until after the fourth vaccination at 14 weeks. Assays used were proliferation assay with 5T4-Fc fusion protein, overlapping 32mer 5T4 peptides, MVA-LacZ and MVA-5T4 infected autologous monocytes. Responses to 5T4 protein or one or more peptide pools were pre-existing in 12/20 patients and subsequently 10 and 12 patients showed boosted and/or de novo responses, respectively. Cumulatively, 13/20 patients showed proliferative responses by week 14. We also assessed the levels of systemic T regulatory cells, plasma cytokine levels, phenotype of tumour-infiltrating lymphocytes including T regulatory cells and tumour HLA class I loss of expression. More than half of the patients showed phenotypes consistent with relative immune suppression and/or escape highlighting the complexity of positive and negative factors challenging any simple correlation with clinical outcome.

KW - 5T4

KW - Colorecta cancer

KW - Immune evasion

KW - T regulatory cell

KW - TroVax

UR - http://www.scopus.com/inward/record.url?scp=68549110430&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=68549110430&partnerID=8YFLogxK

U2 - 10.1007/s00262-009-0674-y

DO - 10.1007/s00262-009-0674-y

M3 - Article

VL - 58

SP - 1657

EP - 1667

JO - Cancer Immunology and Immunotherapy

JF - Cancer Immunology and Immunotherapy

SN - 0340-7004

IS - 10

ER -