Conjugation of new DNA vaccine with polyethylenimine induces cellular immune response and tumor regression in neuroblastoma mouse model
Summary. Aim: 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...
Gespeichert in:
| Datum: | 2023 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | English |
| Veröffentlicht: |
PH Akademperiodyka
2023
|
| Schlagworte: | |
| Online Zugang: | https://exp-oncology.com.ua/index.php/Exp/article/view/2020-2-11 |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| Назва журналу: | Experimental Oncology |
Institution
Experimental Oncology| Zusammenfassung: | Summary. Aim: 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. |
|---|