title: Buccal injection of synthetic HPV long peptide vaccine induces local and systemic antigen-specific CD8+ T-cell immune responses and antitumor effects without adjuvant.
abstract: BACKGROUND
  Human Papillomavirus is responsible for over 99 % of cervical cancers and is associated with cancers of the head and neck. The currently available prophylactic vaccines against HPV do not generate therapeutic effects against established HPV infections and associated lesions and disease. Thus, the need for a therapeutic vaccine capable of treating HPV-induced malignancies persists. Synthetic long peptides vaccination is a popular antigen delivery method because of its safety, stability, production feasibility, and its need to be processed by professional antigen presenting cells before it can be presented to cytotoxic CD8+ T lymphocytes. Cancers in the buccal mucosa have been shown to elicit cancer-related inflammations that are capable of recruiting inflammatory and immune cells to generate antitumor effects. In the current study, we evaluated the therapeutic potential of synthetic HPV long peptide vaccination in the absence of adjuvant in the TC-1 buccal tumor model.
  
  
  RESULTS
  We show that intratumoral vaccination with E7 long peptide alone effectively controls buccal TC-1 tumors in mice. Furthermore, we observed an increase in systemic as well as local E7-specific CD8+ T cells in buccal tumor-bearing mice following the vaccination. Finally, we show that induction of immune responses against buccal tumors by intratumoral E7 long peptide vaccination is independent of CD4+ T cells, and that the phenomenon may be related to the unique environment associated with mucosal tissues.
  
  
  CONCLUSIONS
  Our results suggest the possibility for clinical translation of the administration of adjuvant free therapeutic long peptide vaccine as a potentially effective and safe strategy for mucosal HPV-associated tumor treatment.
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD USA ; Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan China.
authors.forename: Ming-Chieh
authors.initials: MC
authors.lastname: Yang
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Yang
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD USA ; Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD USA.
authors.forename: Liangmei
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD USA.
authors.forename: Ya-Chea
authors.initials: YC
authors.lastname: Tsai
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Jeang
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD USA ; Department of Obstetrics and Gynecology, Johns Hopkins Medical Institutions, Baltimore, MD USA ; Department of Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, MD USA ; Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD USA.
authors.forename: T-C
authors.initials: TC
authors.lastname: Wu
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD USA ; Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD USA ; Departments of Pathology and Oncology, The Johns Hopkins University School of Medicine, CRB II Room 307, 1550 Orleans Street, Baltimore, MD 21231 USA.
authors.forename: Chien-Fu
authors.initials: CF
authors.lastname: Hung
keywords: Adjuvant free; Buccal tumor; E7 long peptide; Immunotherapy