Conjugation of new DNA vaccine with polyethylenimine induces cellular immune response and tumor regression in neuroblastoma mouse model
DOI:
https://doi.org/10.32471/exp-oncology.2312-8852.vol-42-no-2.14473Keywords:
DNA vaccine, neuroblastoma, polyethylenimine, tyrosine hydroxylaseAbstract
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.
References
Brodeur GM. Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer 2003; 3: 203–16.
Hayat MA. Neuroblastoma. New Jersey: Springer, 2012. 281 p.
Smith V, Foster J. High-risk neuroblastoma treatment review. Children (Basel) 2018; 5: 1–7.
Melero G, Gaudernack W, Gerritsen C, et al. Therapeutic vaccines for cancer: an overview if clinical trials. Nat Rev Clin Oncol 2014; 2014: 1–12.
Stevenson FK, Ottensmeier CH, Johnson P, et al. DNA vaccines to attack cancer. Proc Nat Acad Sci USA 2004; 101: 14646–52.
Vatakis D, McMillan M. The signal peptide sequence impacts the immune response elicited by a DNA epitope vaccine. Clin Vaccine Immunol 2011; 18: 1776–80.
Wang G, Pan Li, Zhang Y. Approaches to improved targeting of DNA vaccines. Human Vaccines 2011; 7: 1271–81.
Zhang M, Obata C, Hisaeda H, et al. A novel DNA vaccine based on ubiquitin-proteasome pathway targeting “self”-antigens expressed in melanoma/melanocyte. Gene Therapy 2005; 12: 1049–57.
Lode HN, Huebener N, Zeng Y, et al. DNA minigene vaccination for adjuvant neuroblastoma therapy. Ann NY Acad Sci 2014; 1028: 113–21.
Huebener N, Fest S, Strandsby A, et al. A rationally designed tyrosine hydroxylase DNA vaccine induces specific antineuroblastoma immunity. Mol Cancer Ther 2008; 7: 2241–51.
Huebener N, Fest S, Hilt K, et al. Xenogeneic immunization with human tyrosine hydroxylase DNA vaccines suppresses growth of established neuroblastoma. Mol Cancer Ther 2009; 8: 2392–401.
Pession A, Libri V, Sartini R, et al. Real-time RT-PCR of tyrosine hydroxylase to detect bone marrow involvement in advanced neuroblastoma. Oncol Rep 2003; 10: 357–62.
van den Berg JH, Nuijen B, Schumacher TN, et al. Synthetic vehicles for DNA vaccination. J Drug Target 2010; 18: 1–14.
Godbey WT, Wu KK, Mikos AG. Tracking the intracellular path of poly(ethylenimine)/DNA complexes for gene delivery. Proc Nat Acad Sci USA 1999; 96: 5177–81.
Boussif O, Lezoualc’h F, Zanta MA, et al. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. Proc Nat Acad Sci USA 1995; 92: 7297–301.
Grant EV, Thomas M, Fortune J, et al. Enhancement of plasmid DNA immunogenicity with linear polyethylenimine. Eur J Immunol 2012; 42: 2937–48.
Stegantseva MV, Shinkevich VA, Vashkevich KP, et al. Polyethylenimine increases the immunogenicity of DNA-vaccine based on the thyrosine hydroxylase gene in the mouse model of neuroblastoma. Proc Nat Acad Sci of Belarus, Medical series 2018; 15: 323–30 (in Russian).
Widera G, Austin M, Rabussay D. Increased DNA vaccine delivery and immunogenicity by electroporation in vivo. J Immunol 2000; 164: 4635–40.
Herweijer H, Wolff JA. Progress and prospects: naked DNA gene transfer and therapy. Gene Therapy 2003; 10: 453–8.
Shen C, Li J, Zhang Y, et al. Polyethylenimine-based micro/nanoparticles as vaccine adjuvants. Int J Nanomedicine 2016; 12: 5443–60.
Leclerq S, Harms JS, Rosinha GMC, et al. Induction of a Th-1 type immune response but not protective immunity by intramuscular DNA immunization with Brucella abortus GroEL heat-shock gene. J Med Microbiol 2002; 51: 20–6.
Oliveira SC, Rosinha GMS, de-Brito CFA, et al. Immunological properties of gene vaccines delivered by different routes. Braz J Med Biol Res 1999; 32: 207–14.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Experimental Oncology
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
