In vivo responses to vaccination with Mage-b, GM-CSF and thioglycollate in a highly metastatic mouse breast tumor model, 4T1

Claudia Gravekamp, Belinda Leal, Ashley Denny, Rumana Bahar, Shellye Lampkin, Francisco Castro, Sun Hee Kim, Dan Moore, Robert Reddick

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Metastatic breast cancer is an important contributor to morbidity and mortality. Hence, new therapies are needed that target breast cancer metastases. Here, we focus on Mage-b as a possible vaccine target to prevent the development of breast cancer metastases, through activation of Mage-b-specific cytotoxic T lymphocytes (CTL). The syngeneic cell line 4T1, highly expressing Mage-b, was used as a pre-clinical metastatic mouse breast tumor model. BALB/c mice received three preventive intraperitoneal immunizations with Mage-b DNA vaccine mixed with plasmid DNA, secreting granulocyte-macrophage colony stimulating factor (GM-CSF). In addition, antigen-presenting cells were more efficiently recruited to the peritoneal cavity by the injection of thioglycollate broth (TGB), prior to each immunization. Immunization with Mage-b/GM-CSF/TGB significantly reduced the number of metastases by 67% compared to the saline/GM-CSF/TGB and by 69% compared to the vector control/GM-CSF/TGB. Also, tumor growth was significantly reduced by 45% in mice vaccinated with Mage-b/GM-CSF/TGB compared to the saline/GM-CSF/TGB and by 47% compared to the control vector/GM-CSF/TGB group. In vivo, the number of CD8 T cells significantly increased in the primary tumors and metastases of mice vaccinated with Mage-b/GM-CSF/TGB compared to the saline/GM-CSF/TGB and the control vector/GM-CSF/TGB group, while the number of CD4 T cells significantly decreased. The combination of Mage-b, GM-CSF and TGB did not only induce significantly higher levels of IFNγ in the lymph nodes of vaccinated compared to control mice, but also induced significantly higher expression levels of Fas-ligand (FasL) in the primary tumors (expressing Fas protein constitutively), compared to the control mice. Whether the interaction between Fas and FasL may have contributed to the smaller tumors needs to be further analyzed.

Original languageEnglish (US)
Pages (from-to)1067-1077
Number of pages11
JournalCancer Immunology, Immunotherapy
Volume57
Issue number7
DOIs
StatePublished - Jul 2008
Externally publishedYes

Fingerprint

Thioglycolates
Granulocyte-Macrophage Colony-Stimulating Factor
Vaccination
Breast Neoplasms
Neoplasm Metastasis
Immunization
Fas Ligand Protein
Neoplasms
T-Lymphocytes
DNA Vaccines
Peritoneal Cavity
Cytotoxic T-Lymphocytes
Antigen-Presenting Cells
Plasmids
Vaccines
Lymph Nodes

Keywords

  • 4T1
  • Breast tumor model
  • GM-CSF
  • Mage-b DNA vaccine
  • Metastases
  • Thioglycollate

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Oncology

Cite this

In vivo responses to vaccination with Mage-b, GM-CSF and thioglycollate in a highly metastatic mouse breast tumor model, 4T1. / Gravekamp, Claudia; Leal, Belinda; Denny, Ashley; Bahar, Rumana; Lampkin, Shellye; Castro, Francisco; Kim, Sun Hee; Moore, Dan; Reddick, Robert.

In: Cancer Immunology, Immunotherapy, Vol. 57, No. 7, 07.2008, p. 1067-1077.

Research output: Contribution to journalArticle

Gravekamp, Claudia ; Leal, Belinda ; Denny, Ashley ; Bahar, Rumana ; Lampkin, Shellye ; Castro, Francisco ; Kim, Sun Hee ; Moore, Dan ; Reddick, Robert. / In vivo responses to vaccination with Mage-b, GM-CSF and thioglycollate in a highly metastatic mouse breast tumor model, 4T1. In: Cancer Immunology, Immunotherapy. 2008 ; Vol. 57, No. 7. pp. 1067-1077.
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abstract = "Metastatic breast cancer is an important contributor to morbidity and mortality. Hence, new therapies are needed that target breast cancer metastases. Here, we focus on Mage-b as a possible vaccine target to prevent the development of breast cancer metastases, through activation of Mage-b-specific cytotoxic T lymphocytes (CTL). The syngeneic cell line 4T1, highly expressing Mage-b, was used as a pre-clinical metastatic mouse breast tumor model. BALB/c mice received three preventive intraperitoneal immunizations with Mage-b DNA vaccine mixed with plasmid DNA, secreting granulocyte-macrophage colony stimulating factor (GM-CSF). In addition, antigen-presenting cells were more efficiently recruited to the peritoneal cavity by the injection of thioglycollate broth (TGB), prior to each immunization. Immunization with Mage-b/GM-CSF/TGB significantly reduced the number of metastases by 67{\%} compared to the saline/GM-CSF/TGB and by 69{\%} compared to the vector control/GM-CSF/TGB. Also, tumor growth was significantly reduced by 45{\%} in mice vaccinated with Mage-b/GM-CSF/TGB compared to the saline/GM-CSF/TGB and by 47{\%} compared to the control vector/GM-CSF/TGB group. In vivo, the number of CD8 T cells significantly increased in the primary tumors and metastases of mice vaccinated with Mage-b/GM-CSF/TGB compared to the saline/GM-CSF/TGB and the control vector/GM-CSF/TGB group, while the number of CD4 T cells significantly decreased. The combination of Mage-b, GM-CSF and TGB did not only induce significantly higher levels of IFNγ in the lymph nodes of vaccinated compared to control mice, but also induced significantly higher expression levels of Fas-ligand (FasL) in the primary tumors (expressing Fas protein constitutively), compared to the control mice. Whether the interaction between Fas and FasL may have contributed to the smaller tumors needs to be further analyzed.",
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