Induction of Tumor-Specific Cytotoxic T Lymphocytes in Cancer Patients by Autologous Tumor RNA-transfected Dendritic Cells

Ann Surg. 2002 Apr;235(4):540-9. doi: 10.1097/00000658-200204000-00013.

Abstract

Objective: To demonstrate the feasibility of inducing tumor antigen-specific immune responses in patients with metastatic cancer using total tumor RNA-loaded dendritic cells (DCs).

Summary background data: The authors have shown that DCs transfected with mRNA encoding defined tumor antigens induce tumor antigen-specific T-cell responses in vitro and in vivo. There may be significant advantages to inducing immune responses against the entire repertoire of antigens expressed by a patient's autologous tumor.

Methods: RNA was extracted from a metastatic colon cancer and used to load autologous DCs. The DCs were coincubated with autologous T cells and the cytolytic activity of the T cells was assessed by the ability to lyse the autologous tumor cells. RNA was then extracted from a metastatic lung cancer and used to load autologous DCs, followed by four injections of the DC vaccine given every 4 weeks. Tumor antigen-specific cytotoxic T lymphocyte activity was then evaluated by testing peripheral blood mononuclear cells for their ability to lyse an antigen-expressing target.

Results: DCs transfected with the total RNA content of autologous tumor cells stimulated antigen-specific T-cell responses that are capable of recognizing and lysing autologous, primary tumor cells in vitro. Tumor-specific immune responses were induced in a patient with a carcinoembryonic antigen-expressing adenocarcinoma after immunization with autologous DCs transfected with total tumor RNA.

Conclusions: DCs transfected with total tumor RNA may represent a method for inducing immune responses against the entire repertoire of tumor antigens of surgically resected malignancies.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / immunology*
  • Adenocarcinoma / secondary
  • Adenocarcinoma / therapy
  • Aged
  • Antigens, Neoplasm / immunology*
  • Colonic Neoplasms / immunology*
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / therapy
  • Dendritic Cells / immunology*
  • Feasibility Studies
  • Humans
  • Immunotherapy, Active
  • In Vitro Techniques
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy
  • Male
  • Melanoma / immunology*
  • Melanoma / secondary
  • Melanoma / therapy
  • Middle Aged
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transfection
  • Tumor Cells, Cultured / immunology

Substances

  • Antigens, Neoplasm