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
Journal
Clinical Cancer Research
Journal Volume
10
Journal Issue
8
Pages
2645-2651
Date Issued
2004
Author(s)
Liu K.-J.
Wang C.-C.
Chen L.-T.
Lin D.-T.
Wu Y.-C.
Yu W.-L.
Hung Y.-M.
Yang H.-Y.
Juang S.-H.
Whang-Peng J.
Abstract
Purpose: 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. Experimental Design: 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 α 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.
SDGs
Other Subjects
carcinoembryonic antigen; fluorouracil; granulocyte macrophage colony stimulating factor; HLA A antigen; interleukin 4; irinotecan; oxaliplatin; peptide derivative; threonyltyrosylalanylcysteinylphenylalanylvalylserylasparaginylleucine; tumor necrosis factor alpha; tyrosylleucylserylglycylalanylasparaginylleucylasparaginylleucine; unclassified drug; adult; aged; article; autoimmunity; cancer combination chemotherapy; cancer immunization; cancer patient; cancer staging; cell culture; cell maturation; clinical article; clinical trial; colorectal carcinoma; controlled clinical trial; controlled study; dendritic cell; drug safety; echography; female; fever; genotype; human; immune response; inguinal lymph node; male; metastasis; mononuclear cell; priority journal; side effect; statistical significance; T lymphocyte; treatment outcome; vaccination; Adult; Aged; Cancer Vaccines; Carcinoembryonic Antigen; Cells, Cultured; Colorectal Neoplasms; Dendritic Cells; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Genotype; Granulocyte-Macrophage Colony-Stimulating Factor; HLA-A Antigens; Humans; Immunotherapy; Interferon Type II; Leukocytes, Mononuclear; Male; Middle Aged; Peptides; T-Lymphocytes; Time Factors
Type
journal article