Article
作者: Mohammed, Omar J ; Coble, Vincent L ; Adams, Sally E ; Durrant, Lindy G ; Lynn, Geoffrey M ; Uddin, Nazim ; Zhu, Yaling ; Ranglani, Priscilla ; Parry, Adrian ; Wright, Alissa ; Brentville, Victoria A ; Al-Omari, Abdullah A ; Cook, Katherine W ; Skinner, Anne ; Symonds, Peter ; Choudhury, Ruhul H
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 (SNAPvaxTM) 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.
