Cancer Immunology, Immunotherapy

, Volume 59, Issue 11, pp 1727–1737 | Cite as

Human papillomavirus type 16 E6-specific antitumor immunity is induced by oral administration of HPV16 E6-expressing Lactobacillus casei in C57BL/6 mice

  • Tae-Young Lee
  • Yang-Hyun Kim
  • Kyung-Soon Lee
  • Jeong-Ki Kim
  • Il-Han Lee
  • Jai-Myung Yang
  • Moon-Hee Sung
  • Jong-Sup Park
  • Haryoung Poo
Original Article

Abstract

Given that local cell-mediated immunity (CMI) against the human papillomavirus type 16 E6 (HPV16 E6) protein is important for eradication of HPV16 E6-expressing cancer cells in the cervical mucosa, the HPV16 E6 protein may be a target for the mucosal immunotherapy of cervical cancer. Here, we expressed the HPV16 E6 antigen on Lactobacillus casei (L. casei) and investigated E6-specific CMI following oral administration of the L. casei-PgsA-E6 to mice. Surface expression of HPV16 E6 antigens was confirmed and mice were orally inoculated with the L. casei-PgsA or the L. casei-PgsA-E6. Compared to the L. casei-PgsA-treated mice, significantly higher levels of serum IgG and mucosal IgA were observed in L. casei-PgsA-E6-immunized mice; these differences were significantly enhanced after boost. Consistent with this, systemic and local CMI were significantly increased after the boost, as shown by increased counts of IFN-γ-secreting cells in splenocytes, mesenteric lymph nodes (MLN), and vaginal samples. Furthermore, in the TC-1 tumor model, animals receiving the orally administered L. casei-PgsA-E6 showed reduced tumor size and increased survival rate versus mice receiving control (L. casei-PgsA) immunization. We also found that L. casei-PgsA-E6-induced antitumor effect was decreased by in vivo depletion of CD4+ or CD8+ T cells. Collectively, these results indicate that the oral administration of lactobacilli bearing the surface-displayed E6 protein induces T cell-mediated cellular immunity and antitumor effects in mice.

Keywords

HPV16 E6 Lactobacillus casei Antitumor effect PgsA Cell-mediated immunity 

Abbreviations

HPV

Human papillomavirus

PgsA

Poly-gamma-glutamic acid synthetase complex A

IFN-γ

Interferon gamma

ELISA

Enzyme-linked immunosorbent assay

ELISPOT

Enzyme-linked immunospot

SD

Standard deviation

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Tae-Young Lee
    • 1
  • Yang-Hyun Kim
    • 1
  • Kyung-Soon Lee
    • 1
  • Jeong-Ki Kim
    • 1
  • Il-Han Lee
    • 2
  • Jai-Myung Yang
    • 3
  • Moon-Hee Sung
    • 4
  • Jong-Sup Park
    • 5
  • Haryoung Poo
    • 1
  1. 1.Viral Infectious Disease Research CenterKorea Research Institute of Bioscience and BiotechnologyDaejonKorea
  2. 2.Bioleaders CorporationDaejeonKorea
  3. 3.Department of Biological SciencesSogang UniversitySeoulKorea
  4. 4.Department of Bio and NanochemistryKookmin UniversitySeoulKorea
  5. 5.Department of Obstetrics and GynecologyThe Catholic UniversitySeoulKorea

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