Conjugation of new DNA vaccine with polyethylenimine induces cellular immune response and tumor regression in neuroblastoma mouse model / M. V. Stegantseva [et al.] // Experimental Oncology. - 2020. - Том 42, N 2. - P120-125 MeSH-главная: НЕЙРОБЛАСТОМА -- NEUROBLASTOMA (иммунология, патофизиология) Аннотация: To estimate immunogenicity and antitumor effect of new DNA vaccine against neuroblastoma using tyrosine hydroxylase as an antigen and linear polyethylenimine (PEI) 20 kDa as a synthetic DNA carrier in syngeneic mouse tumor model. Materials and Methods: DNA vaccine was made by cloning the tyrosine hydroxylase minigene fused to the potato virus X coat protein gene into the expression vector. The A/J mice were vaccinated by three intramuscular injections. For immunogenicity study, immune response was estimated by target cells cytotoxicity assay, interferon-gamma production in enzyme-linked immunospot assay and antigen-specific antibodies in 14 days after the final vaccination. Antitumor effect was assessed by measurement of tumor volume and event-free survival rate in mice with engrafted NB41A3 murine neuroblastoma cells following three intramuscular injections of the vaccine: 7 days before, 5 and 10 days after tumor engraftment. The immune response was also assessed on the 30th day after tumor engraftment. Results: The immunogenicity and antitumor effect of the vaccine in the form of aqueous solution of DNA and DNA-PEI conjugate were compared. Splenocytes cytotoxicity was the highest in the group of DNA-PEI vaccines (37.3 ± 6.9% lysis of target cells) compared with the unconjugated DNA vaccine (26.2 ± 4.0%) and placebo control (21.9 ± 3.7%). The production of interferon-gamma in the enzyme-linked immunospot assay was about ten times higher in the DNA-PEI group than in the other groups. The vaccine slowed or prevented the growth of the tumor. Mice vaccinated with the DNA-PEI vaccine had significantly better survival compared to control group (p 0.0003). Conclusions: DNA vaccine against tyrosine hydroxylase, administered as a DNA-PEI 20 kDa conjugate, slows down the growth of neuroblastoma cells engrafted to mice Доп.точки доступа: Stegantseva, M. V. Shinkevich, V. A. Tumar, E. M. Meleshko, A. N. Свободных экз. нет