Dendritic cells loaded with killed breast cancer cells induce differentiation of tumor-specific cytotoxic T lymphocytes.
BACKGROUND
Early clinical trials, mostly in the setting of melanoma, have shown that dendritic cells (DCs) expressing tumor antigens induce some immune responses and some clinical responses. A major difficulty is the extension to other tumors, such as breast carcinoma, for which few defined tumor-associated antigens are available. We have demonstrated, using both prostate carcinoma and melanoma as model systems, that DCs loaded with killed allogeneic tumor cell lines can induce CD8+ T cells to differentiate into cytotoxic T lymphocytes (CTLs) specific for shared tumor antigens.


METHODS
The present study was designed to determine whether DCs would capture killed breast cancer cells and present their antigens to autologous CD4+ and CD8+ T cells.


RESULTS
We show that killed breast cancer cells are captured by immature DCs that, after induced maturation, can efficiently present MHC class I and class II peptides to CD8+ and CD4+ T lymphocytes. The elicited CTLs are able to kill the target cells without a need for pretreatment with interferon gamma. CTLs can be obtained by culturing the DCs loaded with killed breast cancer cells with unseparated peripheral blood lymphocytes, indicating that the DCs can overcome any potential inhibitory effects of breast cancer cells.


CONCLUSIONS
Loading DCs with killed breast cancer cells may be considered a novel approach to breast cancer immunotherapy and to identification of shared breast cancer antigens.
Neidhardt-Berard
Eve-Marie
EM
Centre Léon-Bérard, Laboratoire de thérapie cellulaire et greffes hématopoiètiques, Lyon, France. neidhard@lyon.fnclcc.fr
Berard
Frederic
F
Banchereau
Jacques
J
Palucka
A Karolina
AK
D017951:Antigen Presentation / Q000502:physiology; D000938:Antigen-Presenting Cells / Q000502:physiology; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D016923:Cell Death / Q000528:radiation effects; D002454:Cell Differentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000378:metabolism / Q000502:physiology*; D018984:Epitopes, T-Lymphocyte / Q000502:physiology; D005720:Gamma Rays; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D020014:K562 Cells / Q000473:pathology; D008213:Lymphocyte Activation / Q000502:physiology*; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*
D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D007371:Interferon-gamma