Therapeutic HPV cancer vaccine targeted to CD40 elicits effective CD8+ T-cell immunity

Wenjie Yin, Dorothee Duluc, Hye Mee Joo, Yaming Xue, Chao Gu, Zhiqing Wang, Lei Wang, Richard Ouedraogo, Lance Oxford, Amelia Clark, Falguni Parikh, Seunghee Kim-Schulze, Lu Ann Thompson-Snipes, Sang Yull Lee, Clay Beauregard, Jung Hee Woo, Sandra Zurawski, Andrew G. Sikora, Gerard Zurawski, Sang Kon Oh

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Human papillomavirus (HPV), particularly HPV16 and HPV18, can cause cancers in diverse anatomical sites, including the anogenital and oropharyngeal (throat) regions. Therefore, development of safe and clinically effective therapeutic vaccines is an important goal. Herein, we show that a recombinant fusion protein of a humanized antibody to CD40 fused to HPV16.E6/7 (αCD40-HPV16.E6/7) can evoke HPV16.E6/7-specific CD8+ and CD4+ T-cell responses in head-and-neck cancer patients in vitro and in human CD40 transgenic (hCD40Tg) mice in vivo. The combination of αCD40-HPV16.E6/7 and poly(I:C) efficiently primed HPV16. E6/7-specific T cells, particularly CD8+ T cells, in hCD40Tg mice. Inclusion of montanide enhanced HPV16.E6/7-specific CD4+, but not CD8+, T-cell responses. Poly(I:C) plus αCD40-HPV16.E6/7 was sufficient to mount both preventative and therapeutic immunity against TC-1 tumors in hCD40Tg mice, significantly increasing the frequency of HPV16-specific CD8+ CTLs in the tumors, but not in peripheral blood. In line with this, tumor volume inversely correlated with the frequency of HPV16.E6/7-specific CD8+ T cells in tumors, but not in blood. These data suggest that CD40-targeting vaccines for HPV-associated malignancies can provide a highly immunogenic platform with a strong likelihood of clinical benefit. Data from this study offer strong support for the development of CD40-targeting vaccines for other cancers in the future.

Original languageEnglish (US)
Pages (from-to)823-834
Number of pages12
JournalCancer Immunology Research
Volume4
Issue number10
DOIs
StatePublished - Oct 2016

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

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    Yin, W., Duluc, D., Joo, H. M., Xue, Y., Gu, C., Wang, Z., Wang, L., Ouedraogo, R., Oxford, L., Clark, A., Parikh, F., Kim-Schulze, S., Thompson-Snipes, L. A., Lee, S. Y., Beauregard, C., Woo, J. H., Zurawski, S., Sikora, A. G., Zurawski, G., & Oh, S. K. (2016). Therapeutic HPV cancer vaccine targeted to CD40 elicits effective CD8+ T-cell immunity. Cancer Immunology Research, 4(10), 823-834. https://doi.org/10.1158/2326-6066.CIR-16-0128