| First Author | Al-Omari AA | Year | 2024 |
| Journal | NPJ Vaccines | Volume | 9 |
| Issue | 1 | Pages | 236 |
| PubMed ID | 39604380 | Mgi Jnum | J:359567 |
| Mgi Id | MGI:7787251 | Doi | 10.1038/s41541-024-01029-1 |
| Citation | Al-Omari AA, et al. (2024) Modi-2 a vaccine stimulating CD4 responses to homocitrullinated self epitopes as therapy for solid cancers. NPJ Vaccines 9(1):236 |
| abstractText | Stresses within the tumour microenvironment can mediate post-translational modifications of self-proteins. Homocitrullination is the conversion of lysine to homocitrulline which generates neoepitopes and bypasses self-tolerance. In this study a vaccine targeting homocitrullinated antigens was assessed for stimulation of anti-tumour immunity. Peptides that bind HLA are often hydrophobic which can complicate large scale manufacture and solubility. Here we demonstrate the self-assembling nanoparticle technology (SNAPvax(TM)) to co-deliver four homocitrullinated peptides and adjuvant in nanoparticles of a precise size and composition as a vaccine ("Modi-2") that is optimized for manufacturing ease and T cell induction. Strong T cell responses and anti-tumour immunity in mouse tumour models was stimulated against against B16 melanoma (p = 0.0113), CT26 colorectal cancer (p < 0.0001) and 4T1 breast cancer (p = 0.0090). We demonstrate that human lung, colorectal, breast and prostate tumours express the Modi-2 target antigens and propose the Modi-2 vaccine has potential for translation into clinic in several cancer indications. |
