A DNA vaccine encoding a codon-optimized human papillomavirus type 16 E6 gene enhances CTL response and anti-tumor activity

Cheng Tao Lin, Ya Chea Tsai, Liangmei He, Roanne Calizo, Hung Hsueh Chou, Ting Chang Chang, Yung Kuei Soong, Chien-Fu Hung, Chyong Huey Lai

Research output: Contribution to journalArticle

Abstract

The HPV oncoproteins E6 and E7 are consistently expressed in HPV-associated cancer cells and are responsible for their malignant transformation. Therefore, HPV E6 and E7 are ideal target antigens for developing vaccines and immunotherapeutic strategies against HPV-associated neoplasms. Recently, it has been demonstrated that codon optimization of the HPV-16 E7 gene resulted in highly efficient translation of E7 and increased the immunogenicity of E7-specific DNA vaccines. Since vaccines targeting E6 also represent an important strategy for controlling HPV-associated lesions, we developed a codon-optimized HPV-16 E6 DNA vaccine (pNGVL4a-E6/opt) and characterized the E6-specific CD8+ T cell immune responses as well as the protective and therapeutic anti-tumor effects in vaccinated C57BL/6 mice. Our data indicated that transfection of human embryonic kidney cells (293 cells) with pNGVL4a-E6/opt resulted in highly efficient translation of E6. In addition, vaccination with pNGVL4a-E6/opt significantly enhanced E6-specific CD8 + T cell immune responses in C57BL/6 mice. Mice vaccinated with pNGVL4a-E6/opt are able to generate potent protective and therapeutic antitumor effects against challenge with E6-expressing tumor cell line, TC-1. Thus, DNA vaccines encoding a codon-optimized HPV-16 E6 may be a promising strategy for improving the potency of prophylactic and therapeutic HPV vaccines with potential clinical implications.

Original languageEnglish (US)
Pages (from-to)481-488
Number of pages8
JournalJournal of Biomedical Science
Volume13
Issue number4
DOIs
StatePublished - Jul 2006

Fingerprint

DNA Vaccines
Human papillomavirus 16
Codon
Tumors
T-cells
Genes
Inbred C57BL Mouse
Vaccines
Cells
T-Lymphocytes
Papillomavirus Vaccines
Neoplasms
Oncogene Proteins
Therapeutic Uses
Tumor Cell Line
Transfection
Vaccination
Kidney
Antigens
Therapeutics

Keywords

  • DNA vaccines
  • E6
  • E7
  • Human Papillomavirus (HPV)

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

A DNA vaccine encoding a codon-optimized human papillomavirus type 16 E6 gene enhances CTL response and anti-tumor activity. / Lin, Cheng Tao; Tsai, Ya Chea; He, Liangmei; Calizo, Roanne; Chou, Hung Hsueh; Chang, Ting Chang; Soong, Yung Kuei; Hung, Chien-Fu; Lai, Chyong Huey.

In: Journal of Biomedical Science, Vol. 13, No. 4, 07.2006, p. 481-488.

Research output: Contribution to journalArticle

Lin, Cheng Tao ; Tsai, Ya Chea ; He, Liangmei ; Calizo, Roanne ; Chou, Hung Hsueh ; Chang, Ting Chang ; Soong, Yung Kuei ; Hung, Chien-Fu ; Lai, Chyong Huey. / A DNA vaccine encoding a codon-optimized human papillomavirus type 16 E6 gene enhances CTL response and anti-tumor activity. In: Journal of Biomedical Science. 2006 ; Vol. 13, No. 4. pp. 481-488.
@article{eb3f60ab2ad342279c6872050ed5fec4,
title = "A DNA vaccine encoding a codon-optimized human papillomavirus type 16 E6 gene enhances CTL response and anti-tumor activity",
abstract = "The HPV oncoproteins E6 and E7 are consistently expressed in HPV-associated cancer cells and are responsible for their malignant transformation. Therefore, HPV E6 and E7 are ideal target antigens for developing vaccines and immunotherapeutic strategies against HPV-associated neoplasms. Recently, it has been demonstrated that codon optimization of the HPV-16 E7 gene resulted in highly efficient translation of E7 and increased the immunogenicity of E7-specific DNA vaccines. Since vaccines targeting E6 also represent an important strategy for controlling HPV-associated lesions, we developed a codon-optimized HPV-16 E6 DNA vaccine (pNGVL4a-E6/opt) and characterized the E6-specific CD8+ T cell immune responses as well as the protective and therapeutic anti-tumor effects in vaccinated C57BL/6 mice. Our data indicated that transfection of human embryonic kidney cells (293 cells) with pNGVL4a-E6/opt resulted in highly efficient translation of E6. In addition, vaccination with pNGVL4a-E6/opt significantly enhanced E6-specific CD8 + T cell immune responses in C57BL/6 mice. Mice vaccinated with pNGVL4a-E6/opt are able to generate potent protective and therapeutic antitumor effects against challenge with E6-expressing tumor cell line, TC-1. Thus, DNA vaccines encoding a codon-optimized HPV-16 E6 may be a promising strategy for improving the potency of prophylactic and therapeutic HPV vaccines with potential clinical implications.",
keywords = "DNA vaccines, E6, E7, Human Papillomavirus (HPV)",
author = "Lin, {Cheng Tao} and Tsai, {Ya Chea} and Liangmei He and Roanne Calizo and Chou, {Hung Hsueh} and Chang, {Ting Chang} and Soong, {Yung Kuei} and Chien-Fu Hung and Lai, {Chyong Huey}",
year = "2006",
month = "7",
doi = "10.1007/s11373-006-9086-6",
language = "English (US)",
volume = "13",
pages = "481--488",
journal = "Journal of Biomedical Science",
issn = "1021-7770",
publisher = "BioMed Central",
number = "4",

}

TY - JOUR

T1 - A DNA vaccine encoding a codon-optimized human papillomavirus type 16 E6 gene enhances CTL response and anti-tumor activity

AU - Lin, Cheng Tao

AU - Tsai, Ya Chea

AU - He, Liangmei

AU - Calizo, Roanne

AU - Chou, Hung Hsueh

AU - Chang, Ting Chang

AU - Soong, Yung Kuei

AU - Hung, Chien-Fu

AU - Lai, Chyong Huey

PY - 2006/7

Y1 - 2006/7

N2 - The HPV oncoproteins E6 and E7 are consistently expressed in HPV-associated cancer cells and are responsible for their malignant transformation. Therefore, HPV E6 and E7 are ideal target antigens for developing vaccines and immunotherapeutic strategies against HPV-associated neoplasms. Recently, it has been demonstrated that codon optimization of the HPV-16 E7 gene resulted in highly efficient translation of E7 and increased the immunogenicity of E7-specific DNA vaccines. Since vaccines targeting E6 also represent an important strategy for controlling HPV-associated lesions, we developed a codon-optimized HPV-16 E6 DNA vaccine (pNGVL4a-E6/opt) and characterized the E6-specific CD8+ T cell immune responses as well as the protective and therapeutic anti-tumor effects in vaccinated C57BL/6 mice. Our data indicated that transfection of human embryonic kidney cells (293 cells) with pNGVL4a-E6/opt resulted in highly efficient translation of E6. In addition, vaccination with pNGVL4a-E6/opt significantly enhanced E6-specific CD8 + T cell immune responses in C57BL/6 mice. Mice vaccinated with pNGVL4a-E6/opt are able to generate potent protective and therapeutic antitumor effects against challenge with E6-expressing tumor cell line, TC-1. Thus, DNA vaccines encoding a codon-optimized HPV-16 E6 may be a promising strategy for improving the potency of prophylactic and therapeutic HPV vaccines with potential clinical implications.

AB - The HPV oncoproteins E6 and E7 are consistently expressed in HPV-associated cancer cells and are responsible for their malignant transformation. Therefore, HPV E6 and E7 are ideal target antigens for developing vaccines and immunotherapeutic strategies against HPV-associated neoplasms. Recently, it has been demonstrated that codon optimization of the HPV-16 E7 gene resulted in highly efficient translation of E7 and increased the immunogenicity of E7-specific DNA vaccines. Since vaccines targeting E6 also represent an important strategy for controlling HPV-associated lesions, we developed a codon-optimized HPV-16 E6 DNA vaccine (pNGVL4a-E6/opt) and characterized the E6-specific CD8+ T cell immune responses as well as the protective and therapeutic anti-tumor effects in vaccinated C57BL/6 mice. Our data indicated that transfection of human embryonic kidney cells (293 cells) with pNGVL4a-E6/opt resulted in highly efficient translation of E6. In addition, vaccination with pNGVL4a-E6/opt significantly enhanced E6-specific CD8 + T cell immune responses in C57BL/6 mice. Mice vaccinated with pNGVL4a-E6/opt are able to generate potent protective and therapeutic antitumor effects against challenge with E6-expressing tumor cell line, TC-1. Thus, DNA vaccines encoding a codon-optimized HPV-16 E6 may be a promising strategy for improving the potency of prophylactic and therapeutic HPV vaccines with potential clinical implications.

KW - DNA vaccines

KW - E6

KW - E7

KW - Human Papillomavirus (HPV)

UR - http://www.scopus.com/inward/record.url?scp=33745684793&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745684793&partnerID=8YFLogxK

U2 - 10.1007/s11373-006-9086-6

DO - 10.1007/s11373-006-9086-6

M3 - Article

C2 - 16649071

AN - SCOPUS:33745684793

VL - 13

SP - 481

EP - 488

JO - Journal of Biomedical Science

JF - Journal of Biomedical Science

SN - 1021-7770

IS - 4

ER -