LMP2-DC Vaccine Elicits Specific EBV-LMP2 Response to Effectively Improve Immunotherapy in Patients with Nasopharyngeal Cancer

Objective To evaluate the safety and effectiveness of a vaccine based on latent membrane protein 2(LMP2)modified dendritic cells(DCs)that boosts specific responses of cytotoxic T lymphocytes(CTLs)to LMP2 before and after intradermal injection in patients with nasopharyngeal carcinoma(NPC).Methods DCs were derived from peripheral blood monocytes of patients with NPC.We prepared LMP2-DCs infected by recombinant adenovirus vector expressing LMP2(rAd-LMP2).NPC patients were immunized with 2×105 LMP2-DCs by intradermal injection at week 0 and after the second and fourth weeks.Specific responses to LMP2 were detected by enzyme-linked immunospot(ELISPOT)assay at week 0 and at the fifth and eighth weeks.Local clinicians performed the follow-up and tracking of patients.Results We demonstrated that DCs derived from monocytes displayed typical DC morphologies;the expression of LMP2 in the LMP2-DCs vaccine was confirmed by immunocytochemical assay.Twenty-nine patients with NPC were enrolled in this clinical trial.The LMP2-DCs vaccine was well tolerated in all of the patients.Boosted responses to LMP2 peptide sub-pools were observed in 18 of the 29 patients with NPC.The follow-up data of 29 immunized patients from April,2010 to April 2015 indicated a five-year survival rate of 94.4%in responders and 45.5%in non-responders.Conclusion In this pilot study,we demonstrated that the LMP2-DCs vaccine is safe and effective in patients with NPC.Specific CTLs responses to LMP2 play a certain role in controlling and preventing the recurrence and metastasis of NPC,which warrants further clinical testing.

New Gene Variants Associated with the Risk of Chronic HBV Infection

Some patients with chronic hepatitis B virus(HBV)infection failed to clear HBV,even persistently continue to produce antibodies to HBV.Here we performed a two stage genome wide association study in a cohort of Chinese patients designed to discover single nucleotide variants that associate with HBV infection and clearance of HBV.The first stage involved genome wide exome sequencing of 101 cases(HBsAg plus anti-HBs positive)compared with 102 control patients(antiHBs positive,HBsAg negative).Over 80%of individual sequences displayed 209 sequence coverage.Adapters,uncertain bases[10%or low-quality base calls([50%)were filtered and compared to the human reference genome hg19.In the second stage,579 chronic HBV infected cases and 439 HBV clearance controls were sequenced with selected genes from the first stage.Although there were no significant associated gene variants in the first stage,two significant gene associations were discovered when the two stages were assessed in a combined analysis.One association showed rs506121-“T”allele[within the dedicator of cytokinesis 8(DOCK8)gene]was higher in chronic HBV infection group than that in clearance group(P=0.002,OR=0.77,95%CI[0.65,0.91]).The second association involved rs2071676—A allele within the Carbonic anhydrase(CA9)gene that was significantly elevated in chronic HBV infection group compared to the clearance group(P=0.0003,OR=1.35,95%CI[1.15,1.58]).Upon replication these gene associations would suggest the influence of DOCK8 and CA9 as potential risk genetic factors in the persistence of HBV infection.