Mucin gene (MUC1) transfected dendritic cells as vaccine: results of a phase I/II clinical trial.
Dendritic cells (DC) derived from peripheral blood monocytes are currently being investigated in clinical trials for their role in stimulating the immune system. We performed a phase I/II clinical trial using human autologous DC transfected with cDNA of the human tumor antigen mucin (MUC1) as a vaccine in 10 patients with advanced breast, pancreatic or papillary cancer. After liposomal transfection, flow cytometry testing showed that 2% to 53% of the DC expressed mucin epitopes. Patients were immunized two or three times with 1 million transfected DC injected subcutaneously (s.c.). A vaccine-specific delayed-type hypersensitivity (DTH) reaction was observed in 3 out of 10 patients. After vaccination, 4 patients showed a 2- to 10-fold increase in the frequency of mucin-specific interferon-gamma (IFN-gamma)-secreting CD8+ T cells. We demonstrated the feasibility and safety of a vaccine consisting of autologous gene-transfected DC, and that immunologic responses could be induced even in patients with pretreated and advanced disease.
Pecher
Gabriele
G
Departmet of Hematology and Oncology, Free University of Berlin, Universitätsklinikum Benjamin Franklin, Berlin, Germany. gabriele.pecher@charite.de
Häring
Arnt
A
Kaiser
Lothar
L
Thiel
Eckhard
E
D000328:Adult; D000368:Aged; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000209:etiology; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000235:genetics*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D014162:Transfection; D014611:Vaccination
D018396:Mucin-1; D007371:Interferon-gamma