Dendritic cells can be rapidly expanded ex vivo and safely administered in patients with metastatic breast cancer.
OBJECTIVE
Immunotherapy using either dendritic cells (DCs) or expanded cytotoxic T cells (CTLs) has received increased interest in the treatment of specific malignancies including metastatic breast cancer (MBC). DCs can be generated ex vivo from monocytes or CD34+ precursors. The ability to expand and safely administer CD34-derived DCs in patients with MBC that have received prior cytotoxic chemotherapy has not been evaluated.


METHODS
We enrolled ten patients with MBC that had received prior chemotherapy for the treatment of metastatic disease on a phase I/II trial designed to test the safety and feasibility of administering ex vivo expanded DCs from CD34+ progenitor cells.


RESULTS
Using a cocktail of multiple different cytokines, we could expand DCs 19-fold compared to the initial CD34-selected product, which allowed the administration of as many as six vaccine treatments per patient. Patients received three to six injections i.v. of DCs pulsed with either the wild type GP2 epitope from the HER-2/neu protein or an altered peptide ligand, isoleucine to leucine (I2L). Toxicity was mild, with no patients demonstrating grade III toxicity during the treatment. Two patients with subcutaneous disease had a partial response to therapy, while IFN-gamma-producing CD8+ T cells could be found in two other patients during treatment.


CONCLUSIONS
This approach is safe and effective in generating a significant quantity of DCs from CD34-precursors.
Dees
E Claire
EC
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Campus Box #7295, Chapel Hill, NC 27599-7295, USA.
McKinnon
Karen P
KP
Kuhns
Jennifer J
JJ
Chwastiak
Kathryn A
KA
Sparks
Scotty
S
Myers
Mary
M
Collins
Edward J
EJ
Frelinger
Jeffrey A
JA
Van Deventer
Henrik
H
Collichio
Frances
F
Carey
Lisa A
LA
Brecher
Mark E
ME
Graham
Mark
M
Earp
H Shelton
HS
Serody
Jonathan S
JS
D000328:Adult; D017951:Antigen Presentation; D018952:Antigens, CD34 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D019496:Cancer Vaccines / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008213:Lymphocyte Activation; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology; D012449:Safety; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination
D018952:Antigens, CD34; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D016207:Cytokines; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases