A Potential Herbal Adjuvant Combined With a Peptide-Based Vaccine Acts Against HPV-Related Tumors Through Enhancing Effector and Memory T-Cell Immune Responses

Front Immunol. 2020 Feb 20:11:62. doi: 10.3389/fimmu.2020.00062. eCollection 2020.

Abstract

Viral infection is associated with many types of tumorigenesis, including human papillomavirus (HPV)-induced cervical cancer. The induction of a specific T-cell response against virus-infected cells is desired to develop an efficient therapeutic approach for virus-associated cancer. Chinese herbal medicine (CHM) has a long history in the treatment of cancer patients in Asian countries. Hedyotis diffusa Willd (Bai Hua She She Cao, BHSSC) is frequently used clinically and has been shown to inhibit tumor growth in vitro. However, in vivo data demonstrating the antitumor efficacy of BHSSC are still lacking. We showed that BHSSC induces murine and human antigen-presenting cell (APC) activation via the MAPK signaling pathway and enhances antigen presentation in bone marrow-derived dendritic cells (BMDCs) in vitro. Furthermore, we identified that treatment with BHSSC leads to improved specific effector and memory T-cell responses in vivo. Variant peptide-based vaccines combined with BHSSC improved antitumor activity in preventive, therapeutic, and recurrent HPV-related tumor models. Furthermore, we showed that rutin, one of the ingredients in BHSSC, induces a strong specific immune response against HPV-related tumors in vivo. In summary, we demonstrated that BHSSC extract and its active compound, rutin, can be used as adjuvants in peptide-based vaccines to increase immunogenicity and to bypass the requirement of a conditional adjuvant.

Keywords: Chinese herbal medicine; Hedyotis diffusa Willd; cervical cancer; human papillomavirus; peptide-based cancer vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Adjuvants, Immunologic / therapeutic use
  • Alphapapillomavirus / immunology*
  • Animals
  • Cancer Vaccines / pharmacology
  • Cancer Vaccines / therapeutic use
  • Drugs, Chinese Herbal / pharmacology*
  • Drugs, Chinese Herbal / therapeutic use
  • Female
  • Human papillomavirus 16 / immunology
  • Human papillomavirus 16 / metabolism
  • Humans
  • Immunologic Memory / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Papillomavirus E7 Proteins / immunology
  • Papillomavirus Infections / complications*
  • Papillomavirus Infections / immunology
  • Papillomavirus Infections / therapy
  • Papillomavirus Vaccines / immunology*
  • Papillomavirus Vaccines / pharmacology
  • Papillomavirus Vaccines / therapeutic use
  • Uterine Cervical Neoplasms / etiology
  • Uterine Cervical Neoplasms / immunology*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / therapy*
  • Vaccines, Subunit

Substances

  • Adjuvants, Immunologic
  • Cancer Vaccines
  • Drugs, Chinese Herbal
  • Papillomavirus E7 Proteins
  • Papillomavirus Vaccines
  • Vaccines, Subunit