Retroviral vector backbone immunogenicity

Identification of cytotoxic T-cell epitopes in retroviral vector-packaging sequences

E. Kondo, Yoshiki Akatsuka, A. Nawa, K. Kuzushima, K. Tsujimura, M. Tanimoto, Y. Kodera, Y. Morishima, K. Kuzuya, T. Takahashi

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Retroviral vectors are the frequently applied gene delivery vehicles for clinical gene therapy, but specificity of the immunogenicity to the protein encoded by the inserted gene of interest is a problem which needs to be overcome. Here, we describe human cytotoxic T-lymphocyte (CTL) clones recognizing epitopes derived from the protein encoded by the retroviral vector backbone, which were established during the course of our attempts to generate CTLs against cytomegalovirus (CMV) or human papilloma virus (HPV) in vitro. In the case of healthy CMV-seronegative donors, CTL lines specific for retrovirally transduced cells were generated in four out of eight donors by stimulating CD8 T cells with CD40-activated B (CD40-B) cells retrovirally transduced with CMV-pp65. Two CTL clones derived from one of the CTL lines were found to recognize epitopes from gag in the context of HLA-B*4403 and -B*4601, respectively. Similarly, an HLA-B*3501-restricted CTL clone from a cervical cancer patient recognized an epitope located in the junctional regions of the gag and pol sequences. These results show that polypeptides encoded by components of the retroviral vector backbone are in fact immunogenic, generating CTLs in vitro in human cells. Thus, potential CTL responses to retroviral products should also be considered in clinical settings.

Original languageEnglish
Pages (from-to)252-258
Number of pages7
JournalGene Therapy
Volume12
Issue number3
DOIs
Publication statusPublished - 01-02-2005
Externally publishedYes

Fingerprint

T-Lymphocyte Epitopes
Cytotoxic T-Lymphocytes
Product Packaging
Cytomegalovirus
Epitopes
HLA-B Antigens
Clone Cells
Papillomaviridae
Tissue Donors
Uterine Cervical Neoplasms
Genetic Therapy
Genes
Proteins
B-Lymphocytes
T-Lymphocytes
Peptides

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Kondo, E., Akatsuka, Y., Nawa, A., Kuzushima, K., Tsujimura, K., Tanimoto, M., ... Takahashi, T. (2005). Retroviral vector backbone immunogenicity: Identification of cytotoxic T-cell epitopes in retroviral vector-packaging sequences. Gene Therapy, 12(3), 252-258. https://doi.org/10.1038/sj.gt.3302406
Kondo, E. ; Akatsuka, Yoshiki ; Nawa, A. ; Kuzushima, K. ; Tsujimura, K. ; Tanimoto, M. ; Kodera, Y. ; Morishima, Y. ; Kuzuya, K. ; Takahashi, T. / Retroviral vector backbone immunogenicity : Identification of cytotoxic T-cell epitopes in retroviral vector-packaging sequences. In: Gene Therapy. 2005 ; Vol. 12, No. 3. pp. 252-258.
@article{8824bf6582f84b83ac4bddb64007ed29,
title = "Retroviral vector backbone immunogenicity: Identification of cytotoxic T-cell epitopes in retroviral vector-packaging sequences",
abstract = "Retroviral vectors are the frequently applied gene delivery vehicles for clinical gene therapy, but specificity of the immunogenicity to the protein encoded by the inserted gene of interest is a problem which needs to be overcome. Here, we describe human cytotoxic T-lymphocyte (CTL) clones recognizing epitopes derived from the protein encoded by the retroviral vector backbone, which were established during the course of our attempts to generate CTLs against cytomegalovirus (CMV) or human papilloma virus (HPV) in vitro. In the case of healthy CMV-seronegative donors, CTL lines specific for retrovirally transduced cells were generated in four out of eight donors by stimulating CD8 T cells with CD40-activated B (CD40-B) cells retrovirally transduced with CMV-pp65. Two CTL clones derived from one of the CTL lines were found to recognize epitopes from gag in the context of HLA-B*4403 and -B*4601, respectively. Similarly, an HLA-B*3501-restricted CTL clone from a cervical cancer patient recognized an epitope located in the junctional regions of the gag and pol sequences. These results show that polypeptides encoded by components of the retroviral vector backbone are in fact immunogenic, generating CTLs in vitro in human cells. Thus, potential CTL responses to retroviral products should also be considered in clinical settings.",
author = "E. Kondo and Yoshiki Akatsuka and A. Nawa and K. Kuzushima and K. Tsujimura and M. Tanimoto and Y. Kodera and Y. Morishima and K. Kuzuya and T. Takahashi",
year = "2005",
month = "2",
day = "1",
doi = "10.1038/sj.gt.3302406",
language = "English",
volume = "12",
pages = "252--258",
journal = "Gene Therapy",
issn = "0969-7128",
publisher = "Nature Publishing Group",
number = "3",

}

Kondo, E, Akatsuka, Y, Nawa, A, Kuzushima, K, Tsujimura, K, Tanimoto, M, Kodera, Y, Morishima, Y, Kuzuya, K & Takahashi, T 2005, 'Retroviral vector backbone immunogenicity: Identification of cytotoxic T-cell epitopes in retroviral vector-packaging sequences', Gene Therapy, vol. 12, no. 3, pp. 252-258. https://doi.org/10.1038/sj.gt.3302406

Retroviral vector backbone immunogenicity : Identification of cytotoxic T-cell epitopes in retroviral vector-packaging sequences. / Kondo, E.; Akatsuka, Yoshiki; Nawa, A.; Kuzushima, K.; Tsujimura, K.; Tanimoto, M.; Kodera, Y.; Morishima, Y.; Kuzuya, K.; Takahashi, T.

In: Gene Therapy, Vol. 12, No. 3, 01.02.2005, p. 252-258.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Retroviral vector backbone immunogenicity

T2 - Identification of cytotoxic T-cell epitopes in retroviral vector-packaging sequences

AU - Kondo, E.

AU - Akatsuka, Yoshiki

AU - Nawa, A.

AU - Kuzushima, K.

AU - Tsujimura, K.

AU - Tanimoto, M.

AU - Kodera, Y.

AU - Morishima, Y.

AU - Kuzuya, K.

AU - Takahashi, T.

PY - 2005/2/1

Y1 - 2005/2/1

N2 - Retroviral vectors are the frequently applied gene delivery vehicles for clinical gene therapy, but specificity of the immunogenicity to the protein encoded by the inserted gene of interest is a problem which needs to be overcome. Here, we describe human cytotoxic T-lymphocyte (CTL) clones recognizing epitopes derived from the protein encoded by the retroviral vector backbone, which were established during the course of our attempts to generate CTLs against cytomegalovirus (CMV) or human papilloma virus (HPV) in vitro. In the case of healthy CMV-seronegative donors, CTL lines specific for retrovirally transduced cells were generated in four out of eight donors by stimulating CD8 T cells with CD40-activated B (CD40-B) cells retrovirally transduced with CMV-pp65. Two CTL clones derived from one of the CTL lines were found to recognize epitopes from gag in the context of HLA-B*4403 and -B*4601, respectively. Similarly, an HLA-B*3501-restricted CTL clone from a cervical cancer patient recognized an epitope located in the junctional regions of the gag and pol sequences. These results show that polypeptides encoded by components of the retroviral vector backbone are in fact immunogenic, generating CTLs in vitro in human cells. Thus, potential CTL responses to retroviral products should also be considered in clinical settings.

AB - Retroviral vectors are the frequently applied gene delivery vehicles for clinical gene therapy, but specificity of the immunogenicity to the protein encoded by the inserted gene of interest is a problem which needs to be overcome. Here, we describe human cytotoxic T-lymphocyte (CTL) clones recognizing epitopes derived from the protein encoded by the retroviral vector backbone, which were established during the course of our attempts to generate CTLs against cytomegalovirus (CMV) or human papilloma virus (HPV) in vitro. In the case of healthy CMV-seronegative donors, CTL lines specific for retrovirally transduced cells were generated in four out of eight donors by stimulating CD8 T cells with CD40-activated B (CD40-B) cells retrovirally transduced with CMV-pp65. Two CTL clones derived from one of the CTL lines were found to recognize epitopes from gag in the context of HLA-B*4403 and -B*4601, respectively. Similarly, an HLA-B*3501-restricted CTL clone from a cervical cancer patient recognized an epitope located in the junctional regions of the gag and pol sequences. These results show that polypeptides encoded by components of the retroviral vector backbone are in fact immunogenic, generating CTLs in vitro in human cells. Thus, potential CTL responses to retroviral products should also be considered in clinical settings.

UR - http://www.scopus.com/inward/record.url?scp=13544263558&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=13544263558&partnerID=8YFLogxK

U2 - 10.1038/sj.gt.3302406

DO - 10.1038/sj.gt.3302406

M3 - Article

VL - 12

SP - 252

EP - 258

JO - Gene Therapy

JF - Gene Therapy

SN - 0969-7128

IS - 3

ER -