PMID- 21187495 OWN - NLM STAT- MEDLINE DCOM- 20110204 LR - 20201212 IS - 1791-7530 (Electronic) IS - 0250-7005 (Linking) VI - 30 IP - 12 DP - 2010 Dec TI - Immunogenicity of dendritic cells pulsed with CEA peptide or transfected with CEA mRNA for vaccination of colorectal cancer patients. PG - 5091-7 AB - 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. PATIENTS AND 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. CONCLUSION: 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. FAU - Lesterhuis, W Joost AU - Lesterhuis WJ AD - Departments of Medical Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands. FAU - De Vries, I Jolanda M AU - De Vries IJ FAU - Schreibelt, G AU - Schreibelt G FAU - Schuurhuis, Danita H AU - Schuurhuis DH FAU - Aarntzen, Erik H AU - Aarntzen EH FAU - De Boer, Annemiek AU - De Boer A FAU - Scharenborg, Nicole M AU - Scharenborg NM FAU - Van De Rakt, Mandy AU - Van De Rakt M FAU - Hesselink, Erik J AU - Hesselink EJ FAU - Figdor, Carl G AU - Figdor CG FAU - Adema, Gosse J AU - Adema GJ FAU - Punt, Cornelis J A AU - Punt CJ LA - eng SI - ClinicalTrials.gov/NCT00228189 PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Greece TA - Anticancer Res JT - Anticancer research JID - 8102988 RN - 0 (Cancer Vaccines) RN - 0 (Carcinoembryonic Antigen) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA-A2 Antigen) RN - 0 (RNA, Messenger) RN - 9013-72-3 (Hemocyanins) RN - FV4Y0JO2CX (keyhole-limpet hemocyanin) SB - IM MH - Cancer Vaccines/administration & dosage/genetics/*immunology MH - Carcinoembryonic Antigen/genetics/*immunology MH - Colorectal Neoplasms/immunology/*therapy MH - Dendritic Cells/*immunology/physiology MH - Epitopes, T-Lymphocyte/immunology MH - HLA-A2 Antigen/immunology MH - Hemocyanins/immunology MH - Humans MH - Immunotherapy, Adoptive/*methods MH - RNA, Messenger/administration & dosage/genetics/immunology MH - T-Lymphocytes/immunology MH - Transfection EDAT- 2010/12/29 06:00 MHDA- 2011/02/05 06:00 CRDT- 2010/12/29 06:00 PHST- 2010/12/29 06:00 [entrez] PHST- 2010/12/29 06:00 [pubmed] PHST- 2011/02/05 06:00 [medline] AID - 30/12/5091 [pii] PST - ppublish SO - Anticancer Res. 2010 Dec;30(12):5091-7.