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

Int J Oncol. 2004 Apr;24(4):909-17.

Abstract

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.

Publication types

  • Clinical Trial

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / secondary
  • Adenocarcinoma / therapy*
  • Adult
  • Aged
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use
  • Carcinoembryonic Antigen / analysis
  • Carcinoembryonic Antigen / immunology
  • Dendritic Cells / immunology*
  • Feasibility Studies
  • Female
  • Gastrointestinal Neoplasms / immunology
  • Gastrointestinal Neoplasms / secondary
  • Gastrointestinal Neoplasms / therapy*
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • HLA-A Antigens / immunology
  • HLA-A24 Antigen
  • Humans
  • Hypersensitivity, Delayed / etiology
  • Immunotherapy*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / therapy*
  • Male
  • Middle Aged
  • T-Lymphocytes, Cytotoxic / immunology*
  • Treatment Outcome

Substances

  • Cancer Vaccines
  • Carcinoembryonic Antigen
  • HLA-A Antigens
  • HLA-A24 Antigen
  • Granulocyte Colony-Stimulating Factor