Induction of tumor-specific cytotoxic T lymphocytes in cancer patients by autologous tumor RNA-transfected dendritic cells.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Nair, SK; Morse, M; Boczkowski, D; Cumming, RI; Vasovic, L; Gilboa, E; Lyerly, HK

Published Date

  • April 2002

Published In

Volume / Issue

  • 235 / 4

Start / End Page

  • 540 - 549

PubMed ID

  • 11923611

International Standard Serial Number (ISSN)

  • 0003-4932

Language

  • eng

Conference Location

  • United States