PMID- 11904734
OWN - NLM
STAT- MEDLINE
DCOM- 20020508
LR  - 20240426
IS  - 0340-7004 (Print)
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Linking)
VI  - 51
IP  - 2
DP  - 2002 Apr
TI  - Immunotherapy of solid cancer using dendritic cells pulsed with the 
      HLA-A24-restricted peptide of carcinoembryonic antigen.
PG  - 99-106
AB  - 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.
FAU - Itoh, Tsuyoshi
AU  - Itoh T
AD  - Department of Digestive Surgery, Kyoto Prefectural University of Medicine, 465 
      Kajii-cho, Kamigyo-ku, Kyoto 602-0841, Japan. tito@koto.kpu-m.ac.jp
FAU - Ueda, Yuji
AU  - Ueda Y
FAU - Kawashima, Ichiro
AU  - Kawashima I
FAU - Nukaya, Ikuei
AU  - Nukaya I
FAU - Fujiwara, Hitoshi
AU  - Fujiwara H
FAU - Fuji, Nobuaki
AU  - Fuji N
FAU - Yamashita, Tetsuro
AU  - Yamashita T
FAU - Yoshimura, Tetsunori
AU  - Yoshimura T
FAU - Okugawa, Kaori
AU  - Okugawa K
FAU - Iwasaki, Tomoko
AU  - Iwasaki T
FAU - Ideno, Mitsuko
AU  - Ideno M
FAU - Takesako, Kazutoh
AU  - Takesako K
FAU - Mitsuhashi, Masakazu
AU  - Mitsuhashi M
FAU - Orita, Kunzo
AU  - Orita K
FAU - Yamagishi, Hisakazu
AU  - Yamagishi H
LA  - eng
PT  - Journal Article
DEP - 20020130
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (Cancer Vaccines)
RN  - 0 (Carcinoembryonic Antigen)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A24 Antigen)
RN  - 0 (Interferon-alpha)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 143011-72-7 (Granulocyte Colony-Stimulating Factor)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adult
MH  - Cancer Vaccines/*immunology
MH  - Carcinoembryonic Antigen/analysis/*immunology
MH  - Dendritic Cells/*immunology
MH  - Female
MH  - Gastrointestinal Neoplasms/immunology/*therapy
MH  - Granulocyte Colony-Stimulating Factor/pharmacology
MH  - HLA-A Antigens/*immunology
MH  - HLA-A24 Antigen
MH  - Humans
MH  - Hypersensitivity, Delayed/etiology
MH  - Immunotherapy/*methods
MH  - Interferon-alpha/administration & dosage
MH  - Interferon-gamma/biosynthesis
MH  - Lung Neoplasms/immunology/*therapy
MH  - Male
MH  - Middle Aged
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Tumor Necrosis Factor-alpha/administration & dosage
PMC - PMC11032765
EDAT- 2002/03/21 10:00
MHDA- 2002/05/09 10:01
PMCR- 2002/01/30
CRDT- 2002/03/21 10:00
PHST- 2001/06/29 00:00 [received]
PHST- 2001/11/27 00:00 [accepted]
PHST- 2002/03/21 10:00 [pubmed]
PHST- 2002/05/09 10:01 [medline]
PHST- 2002/03/21 10:00 [entrez]
PHST- 2002/01/30 00:00 [pmc-release]
AID - 0257 [pii]
AID - 10.1007/s00262-001-0257-z [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2002 Apr;51(2):99-106. doi: 10.1007/s00262-001-0257-z. 
      Epub 2002 Jan 30.