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

Smita K. Nair, Michael Morse, David Boczkowski, R. Ian Cumming, Ljiljana Vasovic, Eli Gilboa, H. Kim Lyerly

Research output: Contribution to journalArticle

162 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)540-549
Number of pages10
JournalAnnals of Surgery
Volume235
Issue number4
DOIs
StatePublished - Apr 9 2002
Externally publishedYes

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Cytotoxic T-Lymphocytes
Dendritic Cells
RNA
Neoplasm Antigens
Neoplasms
T-Lymphocytes
Antigens
Carcinoembryonic Antigen
Colonic Neoplasms
Immunization
Lung Neoplasms
Blood Cells
Adenocarcinoma
Vaccines
Messenger RNA
Injections

ASJC Scopus subject areas

  • Surgery

Cite this

Induction of tumor-specific cytotoxic T lymphocytes in cancer patients by autologous tumor RNA-transfected dendritic cells. / Nair, Smita K.; Morse, Michael; Boczkowski, David; Ian Cumming, R.; Vasovic, Ljiljana; Gilboa, Eli; Kim Lyerly, H.

In: Annals of Surgery, Vol. 235, No. 4, 09.04.2002, p. 540-549.

Research output: Contribution to journalArticle

Nair, Smita K. ; Morse, Michael ; Boczkowski, David ; Ian Cumming, R. ; Vasovic, Ljiljana ; Gilboa, Eli ; Kim Lyerly, H. / Induction of tumor-specific cytotoxic T lymphocytes in cancer patients by autologous tumor RNA-transfected dendritic cells. In: Annals of Surgery. 2002 ; Vol. 235, No. 4. pp. 540-549.
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