Induction of cytotoxic T cell responses and tumor immunity against unrelated tumors using telomerase reverse transcriptase RNA transfected dendritic cells

Smita K. Nair, Axel Heiser, David Boczkowski, Anish Majumdar, Michio Naoe, Jane S. Lebkowski, Johannes Vieweg, Eli Gilboa

Research output: Contribution to journalArticle

320 Citations (Scopus)

Abstract

The polypeptide component of telomerase (TERT) is an attractive candidate for a broadly expressed tumor rejection antigen because telomerase is silent in normal tissues but is reactivated in more than 85% of cancers. Here we show that immunization against TERT induces immunity against tumors of unrelated origin. Immunization of mice with TERT RNA-transfected dendritic cells (DC) stimulated cytotoxic T lymphocytes (CTL), which lysed melanoma and thymoma tumor cells and inhibited the growth of three unrelated tumors in mice of distinct genetic backgrounds. TERT RNA-transfected human DC stimulated TERT-specific CTL in vitro that lysed human tumor cells, including Epstein Barr virus (EBV)-transformed B cells as well as autologous tumor targets from patients with renal and prostate cancer. Tumor RNA-transfected DC were used as surrogate targets in the CTL assays, obviating the difficulties in obtaining tumor cells from cancer patients. In one instance, where a tumor cell line was successfully established in culture from a patient with renal cancer, the patient's tumor cells were efficiently lysed by the CTL. Immunization with tumor RNA was generally more effective than immunization with TERT RNA, suggesting that an optimal immunization protocol may have to include TERT as well as additional tumor antigens.

Original languageEnglish
Pages (from-to)1011-1017
Number of pages7
JournalNature Medicine
Volume6
Issue number9
DOIs
StatePublished - Sep 1 2000
Externally publishedYes

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T-cells
Telomerase
Dendritic Cells
Tumors
Immunity
RNA
T-Lymphocytes
Immunization
Neoplasms
Cells
Cytotoxic T-Lymphocytes
Kidney Neoplasms
Neoplasm Antigens
Thymoma
Tumor Cell Line
Human Herpesvirus 4
Viruses
Cell culture
Melanoma
Assays

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Induction of cytotoxic T cell responses and tumor immunity against unrelated tumors using telomerase reverse transcriptase RNA transfected dendritic cells. / Nair, Smita K.; Heiser, Axel; Boczkowski, David; Majumdar, Anish; Naoe, Michio; Lebkowski, Jane S.; Vieweg, Johannes; Gilboa, Eli.

In: Nature Medicine, Vol. 6, No. 9, 01.09.2000, p. 1011-1017.

Research output: Contribution to journalArticle

Nair, Smita K. ; Heiser, Axel ; Boczkowski, David ; Majumdar, Anish ; Naoe, Michio ; Lebkowski, Jane S. ; Vieweg, Johannes ; Gilboa, Eli. / Induction of cytotoxic T cell responses and tumor immunity against unrelated tumors using telomerase reverse transcriptase RNA transfected dendritic cells. In: Nature Medicine. 2000 ; Vol. 6, No. 9. pp. 1011-1017.
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