title: The Safety and Immunological Effects of rAd5-EBV-LMP2 Vaccine in Nasopharyngeal Carcinoma Patients: A Phase I Clinical Trial and Two-Year Follow-Up.
abstract: Epstein-Barr virus (EBV)-encoded latent membrane protein 2 (LMP2) promotes nasopharyngeal carcinoma (NPC) progression. Previously, we reported that the dendritic cells (DCs) transfected with EBV-LMP2 recombinant serotype 5 adenoviruses (rAd5) induced anti-tumor effect by eliciting cytotoxic T lymphocytes (CTLs)-mediated immune response in vitro and the adenoviral vaccine of EBV-LMP2 (rAd5-EBV-LMP2) stimulated antigen-specific cellular immunity in mice. However, the safety and immunological effect of rAd5-EBV-LMP2 vaccine in human still remained unknown. Here we conducted a single-center, non-randomized, open-label, single-arm phase I clinical trial to clarify this unsolved issue. A total of 24 patients with regional advanced NPC were sequentially enrolled into three dose level groups (2×10(9), 2×10(10), 2×10(11) vp). The rAd5-EBV-LMP2 vaccines were intramuscularly injected for four times within 28 d (D0, D7, D14, D28). Blood samples were harvested immediately before every vaccination, one week and one month after the last vaccination (D0, D7, D14, D28, D35, D58). All the vaccine inoculation-related toxicities presented as grade I/II adverse events. The most frequent systemic adverse reactions were fatigue (33.0%, 8/24), myalgia (29.2%, 7/24) and cough (29.2%, 7/24), while the most common regional adverse reaction was tenderness in the inoculation site (54.2%, 13/24). In addition, proportion of CD(3+)CD(4+) cells in peripheral blood was significantly increased in the high dose group (2×10(11) vp). The rAd5-EBV-LMP2 vaccine was generally well-tolerated and the high dose (2×10(11) vp) is recommended to be adopted in phase II studies. The long-term outcome of rAd5-EBV-LMP2 vaccine inoculation is required to be determined in following placebo-controlled trials.
authors.affiliation: Department of Otolaryngology-Head and Neck Oncology, The People's Hospital of Guangxi Zhuang Autonomous Region.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Si
authors.forename: Zhuoxia
authors.initials: Z
authors.lastname: Deng
authors.forename: Guiping
authors.initials: G
authors.lastname: Lan
authors.forename: Haijun
authors.initials: H
authors.lastname: Du
authors.forename: Yongli
authors.initials: Y
authors.lastname: Wang
authors.forename: Jinyuan
authors.initials: J
authors.lastname: Si
authors.forename: Jiazhang
authors.initials: J
authors.lastname: Wei
authors.forename: Jingjin
authors.initials: J
authors.lastname: Weng
authors.forename: Yangda
authors.initials: Y
authors.lastname: Qin
authors.forename: Bo
authors.initials: B
authors.lastname: Huang
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Qin
mesh_terms: D000328:Adult; D019496:Cancer Vaccines / Q000009:adverse effects* / Q000276:immunology*; D002277:Carcinoma; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000276:immunology* / Q000628:therapy*
chemical_list: D019496:Cancer Vaccines