Mannan-MUC1-pulsed dendritic cell immunotherapy: a phase I trial in patients with adenocarcinoma.
OBJECTIVE
Tumor antigen-loaded dendritic cells show promise for cancer immunotherapy. This phase I study evaluated immunization with autologous dendritic cells pulsed with mannan-MUC1 fusion protein (MFP) to treat patients with advanced malignancy.


METHODS
Eligible patients had adenocarcinoma expressing MUC1, were of performance status 0 to 1, with no autoimmune disease. Patients underwent leukapheresis to generate dendritic cells by culture ex vivo with granulocyte macrophage colony-stimulating factor and interleukin 4 for 5 days. Dendritic cells were then pulsed overnight with MFP and harvested for reinjection. Patients underwent three cycles of leukapheresis and reinjection at monthly intervals. Patients with clinical benefit were able to continue with dendritic cell-MFP immunotherapy.


RESULTS
Ten patients with a range of tumor types were enrolled, with median age of 60 years (range, 33-70 years); eight patients were of performance status 0 and two of performance status 1. Dendritic cell-MFP therapy led to strong T-cell IFNgamma Elispot responses to the vaccine and delayed-type hypersensitivity responses at injection sites in nine patients who completed treatments. Immune responses were sustained at 1 year in monitored patients. Antibody responses were seen in three patients only and were of low titer. Side effects were grade 1 only. Two patients with clearly progressive disease (ovarian and renal carcinoma) at entry were stable after initial therapy and went on to further leukapheresis and dendritic cell-MFP immunotherapy. These two patients have now each completed over 3 years of treatment.


CONCLUSIONS
Immunization produced T-cell responses in all patients with evidence of tumor stabilization in 2 of the 10 advanced cancer patients treated. These data support further clinical evaluation of this dendritic cell-MFP immunotherapy.
Loveland
Bruce E
BE
Austin Research Institute, and Medical Oncology Unit, Austin Hospital, Heidelberg, Melbourne, Victoria, Australia. b.loveland@ari.unimelb.edu.au
Zhao
Anne
A
White
Shane
S
Gan
Hui
H
Hamilton
Kate
K
Xing
Pei-Xiang
PX
Pietersz
Geoffrey A
GA
Apostolopoulos
Vasso
V
Vaughan
Hilary
H
Karanikas
Vaios
V
Kyriakou
Peter
P
McKenzie
Ian F C
IF
Mitchell
Paul L R
PL
D000230:Adenocarcinoma / Q000276:immunology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000633:toxicity; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D007167:Immunotherapy; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007937:Leukapheresis; D008297:Male; D008351:Mannans / Q000008:administration & dosage* / Q000276:immunology / Q000633:toxicity; D008875:Middle Aged; D018396:Mucin-1; D009077:Mucins / Q000008:administration & dosage* / Q000276:immunology; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C060192:MUC1 protein, human; D008351:Mannans; D018396:Mucin-1; D009077:Mucins; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma