Nanoliposomal VEGF-R2 peptide vaccine acts as an effective therapeutic vaccine in a murine B16F10 model of melanoma

Fatemeh Zahedipour; Parvin Zamani; Mohammad Mashreghi; Mojgan Astaneh; Mojtaba Sankian; Atefeh Amiri; Khadijeh Jamialahmadi; Mahmoud Reza Jaafari

doi:10.1186/s12645-023-00213-7

Nanoliposomal VEGF-R2 peptide vaccine acts as an effective therapeutic vaccine in a murine B16F10 model of melanoma

Cancer Nanotechnol. 2023;14(1):62. doi: 10.1186/s12645-023-00213-7. Epub 2023 Jun 14.

Authors

Fatemeh Zahedipour^{1

2}, Parvin Zamani², Mohammad Mashreghi², Mojgan Astaneh², Mojtaba Sankian³, Atefeh Amiri^{1

2}, Khadijeh Jamialahmadi⁴, Mahmoud Reza Jaafari^{2

4

5}

Affiliations

¹ Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
² Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
³ Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
⁴ Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
⁵ Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Abstract

Background: The vascular endothelial growth factor receptor-2 (VEGFR-2) plays an important role in melanoma development and progression. Peptide vaccines have shown great potential in cancer immunotherapy by targeting VEGFR-2 as a tumor-associated antigen and boosting the immune response against both tumor cells and tumor endothelial cells. Despite this, the low efficiency of peptide vaccines has resulted in moderate therapeutic results in the majority of studies. Enhancing the delivery of peptide vaccines using nanoliposomes is an important strategy for improving the efficacy of peptide vaccines. In this regard, we designed VEGFR-2-derived peptides restricted to both mouse MHC I and human HLA-A*02:01 using immunoinformatic tools and selected three peptides representing the highest binding affinities. The peptides were encapsulated in nanoliposomal formulations using the film method plus bath sonication and characterized for their colloidal properties.

Results: The mean diameter of peptide-encapsulated liposomes was around 135 nm, zeta potential of - 17 mV, and encapsulation efficiency of approximately 70%. Then, vaccine formulations were injected subcutaneously in mice bearing B16F10-established melanoma tumors and their efficiency in triggering immunological, and anti-tumor responses was evaluated. Our results represented that one of our designed VEGFR-2 peptide nanoliposomal formulations (Lip-V1) substantially activated CD4⁺ (p < 0.0001) and CD8⁺ (P < 0.001) T cell responses and significantly boosted the production of IFN-γ (P < 0.0001) and IL-4 (P < 0.0001). Furthermore, this formulation led to a significant decrease in tumor volume (P < 0.0001) and enhanced survival (P < 0.05) in mice.

Conclusion: Our findings suggest that the nanoliposomal formulation containing VEGFR-2 peptides could be a promising therapeutic vaccination approach capable of eliciting strong antigen-specific immunologic and anti-tumor responses.

Supplementary information: The online version contains supplementary material available at 10.1186/s12645-023-00213-7.

Keywords: Melanoma; Nanoliposomal vaccine; Peptide vaccine; VEGFR-2.