Transfection of RNA encoding tumor antigens following maturation of dendritic cells and to prolonged presentation of antigen and the generation of high-affinity tumor-reactive cytotoxic T lymphocytes

Xinsheng Liao, Yongqing Li, Chiara Bonini, Smita Nair, Eli Gilboa, Philip D. Greenberg, Cassian Yee

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Common tumor vaccination strategies utilizing peptide-pulsed dendritic cells (DC) are limited to targeting antigens with known epitopes in patients expressing a defined restricting allele and can result in the preferential induction of low-avidity T cells that fail to recognize tumor cells. The use of dendritic cells transfected with RNA encoding tumor antigen offers the prospect of antigen-specific immunization without requiring prior knowledge of the immunogenic epitope or restricting allele, since epitopes from the translated protein are processed by the endogenous antigen-presentation machinery. However, its use in vaccine studies has been limited by low RNA transfection efficiency and the use of immature DC as recipient cells. In this study, we report an RNA transfection strategy that routinely achieves expression in 40-50% of mature DC, which are better stimulator cells. Such RNA-transfected mature DC exhibited a prolonged duration of presentation of immunogenic epitopes compared to peptide-pulsed DC, induced greater frequencies of tumor antigen-specific CTL, and generated a CTL population that exhibited higher target avidity and increased tumor lytic capacity. These studies provide compelling in vitro data supporting the evaluation of RNA-transfected mature DC in vaccination protocols as a means to overcome several obstacles to generating anti-tumor responses in vivo.

Original languageEnglish
Pages (from-to)757-764
Number of pages8
JournalMolecular Therapy
Volume9
Issue number5
DOIs
StatePublished - May 1 2004
Externally publishedYes

Fingerprint

Antigen Presentation
Cytotoxic T-Lymphocytes
Neoplasm Antigens
Dendritic Cells
Transfection
RNA
Epitopes
Neoplasms
Vaccination
Alleles
Antigens
Peptides
Immunization
Vaccines
T-Lymphocytes
Population
Proteins

Keywords

  • Adoptive therapy
  • Cytotoxic T lymphocytes
  • Dendritic cell
  • RNA transfection
  • Vaccine therapy

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Transfection of RNA encoding tumor antigens following maturation of dendritic cells and to prolonged presentation of antigen and the generation of high-affinity tumor-reactive cytotoxic T lymphocytes. / Liao, Xinsheng; Li, Yongqing; Bonini, Chiara; Nair, Smita; Gilboa, Eli; Greenberg, Philip D.; Yee, Cassian.

In: Molecular Therapy, Vol. 9, No. 5, 01.05.2004, p. 757-764.

Research output: Contribution to journalArticle

@article{6875cf908f8a41a6b9e982c3db65d6a0,
title = "Transfection of RNA encoding tumor antigens following maturation of dendritic cells and to prolonged presentation of antigen and the generation of high-affinity tumor-reactive cytotoxic T lymphocytes",
abstract = "Common tumor vaccination strategies utilizing peptide-pulsed dendritic cells (DC) are limited to targeting antigens with known epitopes in patients expressing a defined restricting allele and can result in the preferential induction of low-avidity T cells that fail to recognize tumor cells. The use of dendritic cells transfected with RNA encoding tumor antigen offers the prospect of antigen-specific immunization without requiring prior knowledge of the immunogenic epitope or restricting allele, since epitopes from the translated protein are processed by the endogenous antigen-presentation machinery. However, its use in vaccine studies has been limited by low RNA transfection efficiency and the use of immature DC as recipient cells. In this study, we report an RNA transfection strategy that routinely achieves expression in 40-50{\%} of mature DC, which are better stimulator cells. Such RNA-transfected mature DC exhibited a prolonged duration of presentation of immunogenic epitopes compared to peptide-pulsed DC, induced greater frequencies of tumor antigen-specific CTL, and generated a CTL population that exhibited higher target avidity and increased tumor lytic capacity. These studies provide compelling in vitro data supporting the evaluation of RNA-transfected mature DC in vaccination protocols as a means to overcome several obstacles to generating anti-tumor responses in vivo.",
keywords = "Adoptive therapy, Cytotoxic T lymphocytes, Dendritic cell, RNA transfection, Vaccine therapy",
author = "Xinsheng Liao and Yongqing Li and Chiara Bonini and Smita Nair and Eli Gilboa and Greenberg, {Philip D.} and Cassian Yee",
year = "2004",
month = "5",
day = "1",
doi = "10.1016/j.ymthe.2004.02.011",
language = "English",
volume = "9",
pages = "757--764",
journal = "Molecular Therapy",
issn = "1525-0016",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Transfection of RNA encoding tumor antigens following maturation of dendritic cells and to prolonged presentation of antigen and the generation of high-affinity tumor-reactive cytotoxic T lymphocytes

AU - Liao, Xinsheng

AU - Li, Yongqing

AU - Bonini, Chiara

AU - Nair, Smita

AU - Gilboa, Eli

AU - Greenberg, Philip D.

AU - Yee, Cassian

PY - 2004/5/1

Y1 - 2004/5/1

N2 - Common tumor vaccination strategies utilizing peptide-pulsed dendritic cells (DC) are limited to targeting antigens with known epitopes in patients expressing a defined restricting allele and can result in the preferential induction of low-avidity T cells that fail to recognize tumor cells. The use of dendritic cells transfected with RNA encoding tumor antigen offers the prospect of antigen-specific immunization without requiring prior knowledge of the immunogenic epitope or restricting allele, since epitopes from the translated protein are processed by the endogenous antigen-presentation machinery. However, its use in vaccine studies has been limited by low RNA transfection efficiency and the use of immature DC as recipient cells. In this study, we report an RNA transfection strategy that routinely achieves expression in 40-50% of mature DC, which are better stimulator cells. Such RNA-transfected mature DC exhibited a prolonged duration of presentation of immunogenic epitopes compared to peptide-pulsed DC, induced greater frequencies of tumor antigen-specific CTL, and generated a CTL population that exhibited higher target avidity and increased tumor lytic capacity. These studies provide compelling in vitro data supporting the evaluation of RNA-transfected mature DC in vaccination protocols as a means to overcome several obstacles to generating anti-tumor responses in vivo.

AB - Common tumor vaccination strategies utilizing peptide-pulsed dendritic cells (DC) are limited to targeting antigens with known epitopes in patients expressing a defined restricting allele and can result in the preferential induction of low-avidity T cells that fail to recognize tumor cells. The use of dendritic cells transfected with RNA encoding tumor antigen offers the prospect of antigen-specific immunization without requiring prior knowledge of the immunogenic epitope or restricting allele, since epitopes from the translated protein are processed by the endogenous antigen-presentation machinery. However, its use in vaccine studies has been limited by low RNA transfection efficiency and the use of immature DC as recipient cells. In this study, we report an RNA transfection strategy that routinely achieves expression in 40-50% of mature DC, which are better stimulator cells. Such RNA-transfected mature DC exhibited a prolonged duration of presentation of immunogenic epitopes compared to peptide-pulsed DC, induced greater frequencies of tumor antigen-specific CTL, and generated a CTL population that exhibited higher target avidity and increased tumor lytic capacity. These studies provide compelling in vitro data supporting the evaluation of RNA-transfected mature DC in vaccination protocols as a means to overcome several obstacles to generating anti-tumor responses in vivo.

KW - Adoptive therapy

KW - Cytotoxic T lymphocytes

KW - Dendritic cell

KW - RNA transfection

KW - Vaccine therapy

UR - http://www.scopus.com/inward/record.url?scp=2442680269&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2442680269&partnerID=8YFLogxK

U2 - 10.1016/j.ymthe.2004.02.011

DO - 10.1016/j.ymthe.2004.02.011

M3 - Article

VL - 9

SP - 757

EP - 764

JO - Molecular Therapy

JF - Molecular Therapy

SN - 1525-0016

IS - 5

ER -