title: Generation of carcinoembryonic antigen (CEA)-specific T-cell responses in HLA-A*0201 and HLA-A*2402 late-stage colorectal cancer patients after vaccination with dendritic cells loaded with CEA peptides.
abstract: OBJECTIVE
  We intranodally immunized metastatic colorectal carcinoma patients, who had failed standard chemotherapy, with dendritic cells (DCs) pulsed with HLA-A*0201- or HLA-A*2402-restricted carcinoembryonic antigen (CEA) peptides to evaluate the safety of this treatment and the immune response against CEA peptides before and after the treatment.
  
  
  METHODS
  Six patients with the HLA-A*2402 genotype and 4 patients with the HLA-A*0201 genotype were enrolled. A single CEA peptide (YLSGANLNL) or two CEA peptides (QYSWFVNGTF and TYACFVSNL) were used for patients with the HLA-A*0201 or HLA-A*2402 genotype, respectively. Autologous DCs were generated by culturing adherent mononuclear cells with interleukin 4 and granulocyte macrophage colony-stimulating factor for 6 days. Maturation of DCs was then induced with tumor necrosis factor alpha for 40 h. Mature DCs were pulsed with appropriate CEA peptides for 2 h. After washing, 1 million peptide-pulsed DCs were injected into one inguinal lymph node under sonographic guidance. Each patient received four injections.
  
  
  RESULTS
  No grade II/III toxicity or autoimmunity was observed. An increase in the number of CEA-specific T cells after DC vaccination could be detected in 7 of 10 (70%) patients. Two (20%) patients had stable disease for at least 12 weeks. One of these 2 patients experienced a transient decrease in CEA levels during the treatment period and also had the most significant T-cell response against the immunizing CEA peptides.
  
  
  CONCLUSIONS
  These results suggest that our vaccination procedure can generate or boost specific T-cell responses and may provide clinical benefit in certain cancer patients.
authors.affiliation: Cancer Research Cooperative Laboratory at the National Taiwan University Hospital, Division of Cancer Research, National Health Research Institutes, Taipei, Republic of China.
authors.forename: Ko-Jiunn
authors.initials: KJ
authors.lastname: Liu
authors.forename: Chuan-Cheng
authors.initials: CC
authors.lastname: Wang
authors.forename: Li-Tzong
authors.initials: LT
authors.lastname: Chen
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
authors.forename: Dong-Tsamn
authors.initials: DT
authors.lastname: Lin
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Wu
authors.forename: Wei-Lan
authors.initials: WL
authors.lastname: Yu
authors.forename: Yi-Mei
authors.initials: YM
authors.lastname: Hung
authors.forename: Hui-Yu
authors.initials: HY
authors.lastname: Yang
authors.forename: Shin-Hun
authors.initials: SH
authors.lastname: Juang
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Whang-Peng
mesh_terms: D000328:Adult; D000368:Aged; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D002478:Cells, Cultured; D015179:Colorectal Neoplasms / Q000235:genetics / Q000628:therapy*; D003713:Dendritic Cells / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005838:Genotype; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D015234:HLA-A Antigens / Q000235:genetics*; D015789:HLA-A2 Antigen; D059871:HLA-A24 Antigen; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
chemical_list: D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; C438506:HLA-A*24:02 antigen; D015789:HLA-A2 Antigen; D059871:HLA-A24 Antigen; D010455:Peptides; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor