title: Immunogenicity of dendritic cells pulsed with CEA peptide or transfected with CEA mRNA for vaccination of colorectal cancer patients.
abstract: BACKGROUND
  Dendritic cells (DCs) are the professional antigen-presenting cells of the immune system. We have demonstrated that vaccination of autologous ex vivo cultured DCs results in the induction of tumor-specific immune responses in cancer patients, which correlates with clinical response. Optimization of antigen loading is one of the possibilities for further improving the efficacy of DC vaccination. Theoretically, transfection of DCs with RNA encoding a tumor-specific antigen may induce a broader immune response as compared to the most widely used technique of peptide pulsing.
  
  
  METHODS
  In this clinical study, RNA transfection was compared with peptide pulsing as an antigen loading strategy for DC vaccination. Patients with resectable liver metastases of colorectal cancer were vaccinated intravenously and intradermally 3 times weekly with either carcinoembryogenic antigen (CEA)-derived HLA-A2 binding peptide-loaded or CEA mRNA electroporated DCs prior to surgical resection of the metastases. All DCs were loaded with keyhole limpet hemocyanin (KLH) as a control protein. Evaluation of vaccine-induced immune reactivity consisted of T-cell proliferative responses and B-cell antibody responses against KLH in peripheral blood. CEA reactivity was determined in T-cell cultures of biopsies of post-treatment delayed type hypersensitivity skin tests.
  
  
  RESULTS
  Sixteen patients were included. All patients showed T-cell responses against KLH upon vaccination. CEA peptide-specific T-cells were detected in 8 out of 11 patients in the peptide group, but in none of the 5 patients in the RNA group.
  
  
  CONCLUSIONS
  In our study, DC CEA mRNA transfection was not superior to DC CEA peptide pulsing in the induction of a tumor-specific immune response in colorectal cancer patients.
authors.affiliation: Departments of Medical Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
authors.forename: W Joost
authors.initials: WJ
authors.lastname: Lesterhuis
authors.forename: I Jolanda M
authors.initials: IJ
authors.lastname: De Vries
authors.forename: G
authors.initials: G
authors.lastname: Schreibelt
authors.forename: Danita H
authors.initials: DH
authors.lastname: Schuurhuis
authors.forename: Erik H
authors.initials: EH
authors.lastname: Aarntzen
authors.forename: Annemiek
authors.initials: A
authors.lastname: De Boer
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Scharenborg
authors.forename: Mandy
authors.initials: M
authors.lastname: Van De Rakt
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Hesselink
authors.forename: Carl G
authors.initials: CG
authors.lastname: Figdor
authors.forename: Gosse J
authors.initials: GJ
authors.lastname: Adema
authors.forename: Cornelis J A
authors.initials: CJ
authors.lastname: Punt
mesh_terms: D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000628:therapy*; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D012333:RNA, Messenger / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
chemical_list: D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D012333:RNA, Messenger; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin