Cross-priming of cyclin B1, MUC-1 and survivin-specific CD8+ T cells by dendritic cells loaded with killed allogeneic breast cancer cells.
BACKGROUND
The ability of dendritic cells (DCs) to take up whole tumor cells and process their antigens for presentation to T cells ('cross-priming') is an important mechanism for induction of tumor specific immunity.


METHODS
In vitro generated DCs were loaded with killed allogeneic breast cancer cells and offered to autologous naïve CD8+ T cells in 2-week and/or 3-week cultures. CD8+ T cell differentiation was measured by their capacity to secrete effector cytokines (interferon-gamma) and kill breast cancer cells. Specificity was measured using peptides derived from defined breast cancer antigens.


RESULTS
We found that DCs loaded with killed breast cancer cells can prime naïve CD8+ T cells to differentiate into effector cytotoxic T lymphocytes (CTLs). Importantly, these CTLs primed by DCs loaded with killed HLA-A*0201- breast cancer cells can kill HLA-A*0201+ breast cancer cells. Among the tumor specific CTLs, we found that CTLs specific for HLA-A2 restricted peptides derived from three well known shared breast tumor antigens, namely cyclin B1, MUC-1 and survivin.


CONCLUSIONS
This ability of DCs loaded with killed allogeneic breast cancer cells to elicit multiantigen specific immunity supports their use as vaccines in patients with breast cancer.
Saito
Hiroaki
H
Baylor Institute for Immunology Research, Live Oak, Dallas, Texas 75024, USA.
Dubsky
Peter
P
Dantin
Carole
C
Finn
Olivera J
OJ
Banchereau
Jacques
J
Palucka
A Karolina
AK
D017951:Antigen Presentation / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045142:Cross-Priming / Q000276:immunology*; D019926:Cyclin B / Q000276:immunology; D056744:Cyclin B1; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007371:Interferon-gamma; D008869:Microtubule-Associated Proteins / Q000276:immunology; D018396:Mucin-1; D009077:Mucins / Q000276:immunology; D009363:Neoplasm Proteins / Q000276:immunology; D000077022:Survivin; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D051034:Inhibitor of Apoptosis Proteins; C060192:MUC1 protein, human; D008869:Microtubule-Associated Proteins; D018396:Mucin-1; D009077:Mucins; D009363:Neoplasm Proteins; D000077022:Survivin; D007371:Interferon-gamma