Carcinoembryonic antigen (CEA), an oncofetal
glycoprotein overexpressed in most gastrointestinal and
lung cancers, is a candidate molecule for
cancer immunotherapy. Recently, a CEA-derived 9-mer
peptide, CEA652 (TYACFVSNL), has been identified as the
epitope of cytotoxic T lymphocytes restricted with
human leukocyte antigen (HLA)-A24, which is present in 60% of the Japanese population and in some Caucasians. The authors performed a clinical study of a
vaccine using autologous dendritic cells (DCs) pulsed with CEA652 and adjuvant
cytokines, natural human
interferon alpha (nhuIFN-alpha), and natural human
tumor necrosis factor alpha (nhuTNF-alpha), for the treatment of patients with CEA-expressing advanced metastatic
malignancies. Ten
HLA-A24 patients with advanced digestive tract or
lung cancer were enrolled in the study to assess toxicity, tolerability and immune responses to the
vaccine. DCs were generated from
plastic adherent monocytes of
granulocyte colony-stimulating factor (
G-CSF)-mobilized peripheral blood mononuclear cells (PBMCs) in the presence of
granulocyte/macrophage colony-stimulating factor (
GM-CSF) and
interleukin 4 (IL-4). Generated DCs showing an immature phenotype were loaded with CEA652 and injected into patients intradermally and subcutaneously with 50% of the dose administered by each route every 2 weeks for a total of ten vaccinations. The total dose of administered DCs ranged from 2.7x10(7)cells to 1.6x10(8)cells. Adjuvant
cytokines, i.e., 1x10(6) U/body of nhuIFN-alpha and nhuTNF-alpha, were administered to patients twice a week during the vaccination period. No severe toxicity directly attributable to the treatment was observed, and the
vaccine was well tolerated. In the delayed-type
hypersensitivity (DTH) skin test, two patients showed a positive skin response to
peptide-pulsed DCs after vaccination, although none of the patients tested positive prior to vaccination. In the two patients who showed a positive skin response disease remained stable for 6 and 9 months respectively. These results suggest that active immunization using DCs pulsed with CEA652
peptide in combination with the administration of adjuvant
cytokines is a safe and feasible treatment procedure.