Dendritic cell vaccine immunotherapy of cancer targeting MUC1 mucin.
The use of dendritic cells (DCs) for cancer vaccination is effective in suppressing cancer progression. This is because the DCs play a crucial role in priming tumor-specific immunity efficiently as antigen-presenting cells. In this study, we analyzed the ability of DCs to elicit tumor-specific immunity and clinical effects of DC vaccine immunotherapy targeting MUC1 tumor antigens. DCs from 14 patients with advanced or metastatic breast or lung cancer (9 positive for MUC1 and 5 negative for MUC1) were loaded with MUC1 antigens or tumor lysate and used for therapeutic vaccination. After vaccination, all the MUC1-positive patients acquired antigen-specific immunity whereas only 1 case with MUC1-negative cancer showed the specific immunity. Clinically, marked effects such as reduction in tumor sizes or tumor marker levels or disappearance of malignant pleural effusion were observed in 7 of the 9 MUC1-positive cases. However, MUC1-negative patients did not respond to DC vaccines, with the exception of 1 case with MAGE3-positive lung cancer. Survival of MUC1-positive patients was significantly prolonged in comparison with MUC1-negative patients (mean survival: 16.75 versus 3.80 months, p=0.0101). These data suggest that MUC1 is sufficiently immunogenic to elicit strong anti-tumor immunity as a tumor antigen and that DC vaccines targeting MUC1 are useful for immunotherapy of cancer.
Kontani
Keiichi
K
Department of Surgery, Shiga University of Medical Science, Seta, Otsu 520-2192, Japan. konbat@belle.shiga-med.ac.jp
Taguchi
Osamu
O
Ozaki
Yoshitomo
Y
Hanaoka
Jun
J
Sawai
Satoru
S
Inoue
Shuhei
S
Abe
Hajime
H
Hanasawa
Kazuyoshi
K
Fujino
Shozo
S
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000737:chemistry; D001943:Breast Neoplasms / Q000628:therapy; D019496:Cancer Vaccines; D002462:Cell Membrane / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007700:Kinetics; D008175:Lung Neoplasms / Q000628:therapy; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000737:chemistry* / Q000627:therapeutic use; D009362:Neoplasm Metastasis; D010455:Peptides / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D013997:Time Factors
D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D018396:Mucin-1; D010455:Peptides; D011994:Recombinant Proteins