Dendritic cell-based immunotherapy of cancer with carcinoembryonic antigen-derived, HLA-A24-restricted CTL epitope: Clinical outcomes of 18 patients with metastatic gastrointestinal or lung adenocarcinomas.
We conducted a clinical study of cancer vaccine therapy with dendritic cells (DCs) and HLA-A24-restricted carcinoembryonic antigen (CEA)-derived peptide to assess the feasibility and efficacy of such therapy. Eighteen patients with CEA-expressing metastatic gastrointestinal or lung adenocarcinomas who were positive for human leukocyte antigen (HLA)-A24 were enrolled. DCs were generated from the patients' autologous monocyte-enriched fractions of granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells in the presence of granulocyte/macrophage colony-stimulating factor and interleukin-4. The generated DCs were pulsed with CEA-derived, HLA-A24-restricted 9-mer peptide (CEA652) and injected into the patients intradermally and subcutaneously every 2 weeks. Toxicity and clinical and immunological responses were closely monitored in each patient. No severe toxicity directly attributable to the treatment was observed, and the vaccine was well tolerated. Although no definite tumor shrinkage occurred in any patient, long-term stable disease or marked decreases in the serum CEA level were observed in some patients after therapy. Most of the patients in whom treatment was clinically effective showed a positive skin response to CEA652-pulsed DCs (delayed-type hypersensitivity skin test) and a positive in vitro CTL response to CEA652 peptide after therapy. We conclude that active specific immunotherapy using DCs pulsed with CEA652 is a safe and feasible treatment that is clinically effective in some patients with metastatic gastrointestinal or lung adenocarcinomas. Our results will hopefully encourage further refinement and development of DC-based immunotherapy with HLA-A24-restricted CEA-derived peptide for refractory solid cancers that express CEA.
Ueda
Yuji
Y
Department of Surgery and Oncology of Digestive System, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan. yueda@koto.kpu-m.ac.jp
Itoh
Tsuyoshi
T
Nukaya
Ikuei
I
Kawashima
Ichiro
I
Okugawa
Kaori
K
Yano
Yutaro
Y
Yamamoto
Yoshiki
Y
Naitoh
Kei
K
Shimizu
Keiji
K
Imura
Kenichiro
K
Fuji
Nobuaki
N
Fujiwara
Hitoshi
H
Ochiai
Toshiya
T
Itoi
Hirosumi
H
Sonoyama
Teruhisa
T
Hagiwara
Akeo
A
Takesako
Kazutoh
K
Yamagishi
Hisakazu
H
D000230:Adenocarcinoma / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D002272:Carcinoembryonic Antigen / Q000032:analysis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005240:Feasibility Studies; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D015234:HLA-A Antigens / Q000276:immunology; D059871:HLA-A24 Antigen; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000209:etiology; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D016896:Treatment Outcome
D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D016179:Granulocyte Colony-Stimulating Factor