Study on biological characters of SGC7901 gastric cancer cell-dendritic cell fusion vaccines

AIM： To detect the biological characters of the SGC7901 gastric cancer cell-dendritic cell fusion vaccines.METHODS： The suspending living SGC7901 gastric cancer cells and dendritic cells were induced to be fusioned by polyethylene glycol. Pure fusion cells were obtained by selective culture with the HAT/HT culture systems. The fusion cells were counted at different time points of culture and their growth curves were drawn to reflect their proliferative activities. The fusion cells were also cultured in culture medium to investigate whether they could grow into cell clones. MTT method was used to test the stimulating abilities of the fusion cells on T lymphocytes＇ proliferations. Moreover, the fusion cells were planted into nude mice to observe whether they could grow into new planted tumors in this kind of immunodeficiency animals.RESULTS： The fusion cells had weaker proliferative activity and clone abilities than their parental cells. When they were cultured, the counts of cells did not increase remarkably, nor could they grow into cell clones in culture medium. The fusion cells could not grow into new planted tumors after planted into nude mice. The stimulating abilities of the fusion cells on T lymphocytes＇ proliferations were remarkably increased than their parental dendritic cells. CONCLUSION： The SGC7901 gastric cancer cell-dendritic cell fusion vaccines have much weaker proliferative abilities than their parental cells, but they keep strong abilities to irritate the T lymphocytes and have no abilities to grow into new planted tumors in immunodeficiency animals. These are the biological basis for their antitumor biotherapies.

Immunogenicity and safety of a recombinant fusion protein vaccine(V-01)against coronavirus disease 2019 in healthy adults:a randomized,double-blind,placebo-controlled,phaseⅡtrial

Background:Innovative coronavirus disease 2019(COVID-19)vaccines,with elevated global manufacturing capacity,enhanced safety and efficacy,simplified dosing regimens,and distribution that is less cold chain-dependent,are still global imperatives for tackling the ongoing pandemic.A previous phase I trial indicated that the recombinant COVID-19 vaccine(V-01),which contains a fusion protein(IFN-PADRE-RBD-Fc dimer)as its antigen,is safe and well tolerated,capable of inducing rapid and robust immune responses,and warranted further testing in additional clinical trials.Herein,we aimed to assess the immunogenicity and safety of V-01,providing rationales of appropriate dose regimen for further efficacy study.Methods:A randomized,double-blind,placebo-controlled phaseⅡclinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention(Guangdong,China)in March 2021.Both younger(n=440;18–59 years of age)and older(n=440;≥60 years of age)adult participants in this trial were sequentially recruited into two distinct groups:two-dose regimen group in which participants were randomized either to follow a 10 or 25 mg of V-01 or placebo given intramuscularly 21 days apart(allocation ratio,3:3:1,n=120,120,40 for each regimen,respectively),or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 mg of V-01 or placebo(allocation ratio,3:1,n=120,40,respectively).The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2,and specific binding antibodies to the receptor binding domain(RBD).The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events(AEs)within 30 days after full immunization.Results:V-01 provoked substantial immune responses in the two-dose group,achieving encouragingly high titers of neutralizing antibody and anti-RBDimmunoglobulin,which peaked at day 35(161.9[95%confidence interval[CI]:133.3–196.7]and 149.3[95%CI:123.9–179.9]in 10 and 25 mg V-01 group of younger adults,respectively;111.6[95%CI:89.6–139.1]and 111.1[95%CI:89.2–138.4]in 10 and 25 mg V-01 group of older adults,respectively),and remained high at day 49 after a day-21 second dose;these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients(53.6,95%CI:31.3–91.7).Our preliminary data showthat V-01 is safe andwell tolerated,with reactogenicity predominantly being absent or mild in severity and only one vaccinerelated grade 3 or worse AE being observed within 30 days.The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group:with AEs percentages of 19.2%,25.8%,17.5%in older adults vs.34.2%,23.3%,26.7%in younger adults at the 10,25 mg V-01 two-dose group,and 50 mg V-01 one-dose group,respectively.Conclusions:The vaccine candidate V-01 appears to be safe and immunogenic.The preliminary findings support the advancement of the two-dose,10 mg V-01 regimen to a phaseⅢtrial for a large-scale population-based evaluation of safety and efficacy.