PMID- 15010829 OWN - NLM STAT- MEDLINE DCOM- 20040416 LR - 20111117 IS - 1019-6439 (Print) IS - 1019-6439 (Linking) VI - 24 IP - 4 DP - 2004 Apr TI - 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. PG - 909-17 AB - 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. FAU - Ueda, Yuji AU - Ueda Y AD - 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 FAU - Itoh, Tsuyoshi AU - Itoh T FAU - Nukaya, Ikuei AU - Nukaya I FAU - Kawashima, Ichiro AU - Kawashima I FAU - Okugawa, Kaori AU - Okugawa K FAU - Yano, Yutaro AU - Yano Y FAU - Yamamoto, Yoshiki AU - Yamamoto Y FAU - Naitoh, Kei AU - Naitoh K FAU - Shimizu, Keiji AU - Shimizu K FAU - Imura, Kenichiro AU - Imura K FAU - Fuji, Nobuaki AU - Fuji N FAU - Fujiwara, Hitoshi AU - Fujiwara H FAU - Ochiai, Toshiya AU - Ochiai T FAU - Itoi, Hirosumi AU - Itoi H FAU - Sonoyama, Teruhisa AU - Sonoyama T FAU - Hagiwara, Akeo AU - Hagiwara A FAU - Takesako, Kazutoh AU - Takesako K FAU - Yamagishi, Hisakazu AU - Yamagishi H LA - eng PT - Clinical Trial PT - Journal Article PL - Greece TA - Int J Oncol JT - International journal of oncology JID - 9306042 RN - 0 (Cancer Vaccines) RN - 0 (Carcinoembryonic Antigen) RN - 0 (HLA-A Antigens) RN - 0 (HLA-A24 Antigen) RN - 143011-72-7 (Granulocyte Colony-Stimulating Factor) SB - IM MH - Adenocarcinoma/immunology/secondary/*therapy MH - Adult MH - Aged MH - Cancer Vaccines/immunology/therapeutic use MH - Carcinoembryonic Antigen/analysis/immunology MH - Dendritic Cells/*immunology MH - Feasibility Studies MH - Female MH - Gastrointestinal Neoplasms/immunology/secondary/*therapy MH - Granulocyte Colony-Stimulating Factor/pharmacology MH - HLA-A Antigens/immunology MH - HLA-A24 Antigen MH - Humans MH - Hypersensitivity, Delayed/etiology MH - *Immunotherapy MH - Lung Neoplasms/immunology/*therapy MH - Male MH - Middle Aged MH - T-Lymphocytes, Cytotoxic/*immunology MH - Treatment Outcome EDAT- 2004/03/11 05:00 MHDA- 2004/04/17 05:00 CRDT- 2004/03/11 05:00 PHST- 2004/03/11 05:00 [pubmed] PHST- 2004/04/17 05:00 [medline] PHST- 2004/03/11 05:00 [entrez] PST - ppublish SO - Int J Oncol. 2004 Apr;24(4):909-17.