Fungal mannosylation enhances human papillomavirus 16 E7 therapeutic immunity against TC-1 tumors

  • Authors:
    • Zonglin Wang
    • Cuihua Wei
    • Yanjun Zhang
    • Wei Wang
    • Zheng Zhou
    • Gengfu Xiao
  • View Affiliations

  • Published online on: November 8, 2017     https://doi.org/10.3892/or.2017.6083
  • Pages:425-432
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Abstract

Cervical cancer, resulting from infection with human papillomavirus (HPV)16, remains the fourth most common cancer in women worldwide. Recently, three prophylactic HPV vaccines targeting high-risk HPVs (particularly HPV16 and HPV18) have been implemented to protect younger women. However, individuals with pre-existing infections have no benefit from prophylactic vaccines. Thus, there is an urgent need to develop therapeutic vaccines. HPV16 E7 has been widely utilized as a target for immune therapy of HPV16-associated lesions or cancers, reflecting the sustained existence of this virus in cancerous cells. We developed mannosylated HPV16 E7 (mE7) expressed from Pichia pastoris as a therapeutic vaccine against HPV16-associated cancer. Unmannosylated E7 (E7) was also generated from Pichia pastoris as a control. Mannosylation enhanced the uptake of mE7 by mannose receptors of bone marrow-derived dendritic cells (BMDCs), while the uptake of E7 was unaffected. mE7-uptake BMDCs in vitro induced more IFN-γ secretion by splenocytes of immunized mice than E7. Vaccination of C57BL/6 mice with mE7 combined with adjuvant monophosphoryl lipid A (MPL) elicited stronger Th1 (type 1 T helper cell) responses and E7-specific T cell responses than E7. The mE7 vaccine induced the increased production of IFN-γ, IL-2 and TNF-α, elicited more E7-specific IFN-γ-secreting CD8+ T cells in spleen and peripheral blood mononuclear cells (PMBCs) and promoted stronger E7-specific cytotoxic CD8+ T cell responses compared with E7. Furthermore, TC-1 tumor challenged mice were used to confirm the antitumor activity of the vaccines. As a result, mE7 generated complete antitumor activity against TC-1 tumors, while E7 only provided partial antitumor activity. Taken together, mE7 can be a promising immunotherapy for treating cervical cancer.

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January 2018
Volume 39 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

2016 Impact Factor: 2.662
Ranked #31/217 Oncology
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APA
Wang, Z., Wei, C., Zhang, Y., Wang, W., Zhou, Z., & Xiao, G. (2018). Fungal mannosylation enhances human papillomavirus 16 E7 therapeutic immunity against TC-1 tumors. Oncology Reports, 39, 425-432. https://doi.org/10.3892/or.2017.6083
MLA
Wang, Z., Wei, C., Zhang, Y., Wang, W., Zhou, Z., Xiao, G."Fungal mannosylation enhances human papillomavirus 16 E7 therapeutic immunity against TC-1 tumors". Oncology Reports 39.1 (2018): 425-432.
Chicago
Wang, Z., Wei, C., Zhang, Y., Wang, W., Zhou, Z., Xiao, G."Fungal mannosylation enhances human papillomavirus 16 E7 therapeutic immunity against TC-1 tumors". Oncology Reports 39, no. 1 (2018): 425-432. https://doi.org/10.3892/or.2017.6083