RGD Reference Report - In vivo responses to vaccination with Mage-b, GM-CSF and thioglycollate in a highly metastatic mouse breast tumor model, 4T1. - Rat Genome Database

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

Authors: Gravekamp, C  Leal, B  Denny, A  Bahar, R  Lampkin, S  Castro, F  Kim, SH  Moore, D  Reddick, R 
Citation: Gravekamp C, etal., Cancer Immunol Immunother. 2007 Dec 20;.
RGD ID: 2290047
Pubmed: PMID:18094967   (View Abstract at PubMed)
DOI: DOI:10.1007/s00262-007-0438-5   (Journal Full-text)

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 IFNgamma 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Mammary Neoplasms  ISOFas (Mus musculus)2290047; 2290047 RGD 
Experimental Mammary Neoplasms  IMP 2290047 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Fas  (Fas cell surface death receptor)

Genes (Mus musculus)
Fas  (Fas cell surface death receptor)

Genes (Homo sapiens)
FAS  (Fas cell surface death receptor)


Additional Information