Design of immunogenic and effective multi-epitope DNA vaccines for melanoma

Hyun Il Cho, Esteban Celis

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Plasmid DNA vaccination is an attractive way to elicit T cell responses against infectious agents and tumor cells. DNA constructs can be designed to contain multiple T cell epitopes to generate a diverse immune response to incorporate numerous antigens and to reduce limitations due to MHC restriction into a single entity. We have prepared cDNA plasmid constructs containing several mouse T cell epitopes connected by either furin-sensitive or furin-resistant linkers and studied the effects of a cationic cell-penetrating sequence from HIV-tat. Significant CD8 T cell responses were obtained with multi-epitope DNA vaccines followed by in vivo electroporation regardless of the type of linker used and whether the construct had the HIV-tat sequence. The magnitude of immune responses was very similar to all CD8 T cell epitopes contained within each vaccine construct, indicating the absence of immunodominance. Incorporating a T helper epitope into the constructs increased the T cell responses. Prophylactic and therapeutic antitumor responses against B16 melanoma were obtained using a construct containing epitopes from melanosomal proteins, indicating that this vaccination was successful in generating responses to self-antigens that potentially may be subjected to immune tolerance. These findings are useful for designing DNA vaccines for a multitude of diseases where T lymphocytes play a protective or therapeutic role.

Original languageEnglish (US)
Pages (from-to)343-351
Number of pages9
JournalCancer Immunology, Immunotherapy
Volume61
Issue number3
DOIs
StatePublished - Mar 1 2012
Externally publishedYes

Fingerprint

DNA Vaccines
T-Lymphocyte Epitopes
Epitopes
Melanoma
Furin
T-Lymphocytes
Vaccination
Plasmids
HIV
Immune Tolerance
Experimental Melanomas
Electroporation
DNA
Autoantigens
Vaccines
Complementary DNA
Antigens
Therapeutics
Neoplasms
Proteins

Keywords

  • DNA vaccine
  • Melanoma
  • Multi-epitope
  • Tumor immunity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Cite this

Design of immunogenic and effective multi-epitope DNA vaccines for melanoma. / Cho, Hyun Il; Celis, Esteban.

In: Cancer Immunology, Immunotherapy, Vol. 61, No. 3, 01.03.2012, p. 343-351.

Research output: Contribution to journalArticle

@article{8e5a05a9ec7444d19610fd5bb827509b,
title = "Design of immunogenic and effective multi-epitope DNA vaccines for melanoma",
abstract = "Plasmid DNA vaccination is an attractive way to elicit T cell responses against infectious agents and tumor cells. DNA constructs can be designed to contain multiple T cell epitopes to generate a diverse immune response to incorporate numerous antigens and to reduce limitations due to MHC restriction into a single entity. We have prepared cDNA plasmid constructs containing several mouse T cell epitopes connected by either furin-sensitive or furin-resistant linkers and studied the effects of a cationic cell-penetrating sequence from HIV-tat. Significant CD8 T cell responses were obtained with multi-epitope DNA vaccines followed by in vivo electroporation regardless of the type of linker used and whether the construct had the HIV-tat sequence. The magnitude of immune responses was very similar to all CD8 T cell epitopes contained within each vaccine construct, indicating the absence of immunodominance. Incorporating a T helper epitope into the constructs increased the T cell responses. Prophylactic and therapeutic antitumor responses against B16 melanoma were obtained using a construct containing epitopes from melanosomal proteins, indicating that this vaccination was successful in generating responses to self-antigens that potentially may be subjected to immune tolerance. These findings are useful for designing DNA vaccines for a multitude of diseases where T lymphocytes play a protective or therapeutic role.",
keywords = "DNA vaccine, Melanoma, Multi-epitope, Tumor immunity",
author = "Cho, {Hyun Il} and Esteban Celis",
year = "2012",
month = "3",
day = "1",
doi = "10.1007/s00262-011-1110-7",
language = "English (US)",
volume = "61",
pages = "343--351",
journal = "Cancer Immunology and Immunotherapy",
issn = "0340-7004",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "3",

}

TY - JOUR

T1 - Design of immunogenic and effective multi-epitope DNA vaccines for melanoma

AU - Cho, Hyun Il

AU - Celis, Esteban

PY - 2012/3/1

Y1 - 2012/3/1

N2 - Plasmid DNA vaccination is an attractive way to elicit T cell responses against infectious agents and tumor cells. DNA constructs can be designed to contain multiple T cell epitopes to generate a diverse immune response to incorporate numerous antigens and to reduce limitations due to MHC restriction into a single entity. We have prepared cDNA plasmid constructs containing several mouse T cell epitopes connected by either furin-sensitive or furin-resistant linkers and studied the effects of a cationic cell-penetrating sequence from HIV-tat. Significant CD8 T cell responses were obtained with multi-epitope DNA vaccines followed by in vivo electroporation regardless of the type of linker used and whether the construct had the HIV-tat sequence. The magnitude of immune responses was very similar to all CD8 T cell epitopes contained within each vaccine construct, indicating the absence of immunodominance. Incorporating a T helper epitope into the constructs increased the T cell responses. Prophylactic and therapeutic antitumor responses against B16 melanoma were obtained using a construct containing epitopes from melanosomal proteins, indicating that this vaccination was successful in generating responses to self-antigens that potentially may be subjected to immune tolerance. These findings are useful for designing DNA vaccines for a multitude of diseases where T lymphocytes play a protective or therapeutic role.

AB - Plasmid DNA vaccination is an attractive way to elicit T cell responses against infectious agents and tumor cells. DNA constructs can be designed to contain multiple T cell epitopes to generate a diverse immune response to incorporate numerous antigens and to reduce limitations due to MHC restriction into a single entity. We have prepared cDNA plasmid constructs containing several mouse T cell epitopes connected by either furin-sensitive or furin-resistant linkers and studied the effects of a cationic cell-penetrating sequence from HIV-tat. Significant CD8 T cell responses were obtained with multi-epitope DNA vaccines followed by in vivo electroporation regardless of the type of linker used and whether the construct had the HIV-tat sequence. The magnitude of immune responses was very similar to all CD8 T cell epitopes contained within each vaccine construct, indicating the absence of immunodominance. Incorporating a T helper epitope into the constructs increased the T cell responses. Prophylactic and therapeutic antitumor responses against B16 melanoma were obtained using a construct containing epitopes from melanosomal proteins, indicating that this vaccination was successful in generating responses to self-antigens that potentially may be subjected to immune tolerance. These findings are useful for designing DNA vaccines for a multitude of diseases where T lymphocytes play a protective or therapeutic role.

KW - DNA vaccine

KW - Melanoma

KW - Multi-epitope

KW - Tumor immunity

UR - http://www.scopus.com/inward/record.url?scp=84860799184&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860799184&partnerID=8YFLogxK

U2 - 10.1007/s00262-011-1110-7

DO - 10.1007/s00262-011-1110-7

M3 - Article

C2 - 21915800

AN - SCOPUS:84860799184

VL - 61

SP - 343

EP - 351

JO - Cancer Immunology and Immunotherapy

JF - Cancer Immunology and Immunotherapy

SN - 0340-7004

IS - 3

ER -