Plant viral vaccine delivery as a platform to induce cellular immunity against cancer antigens

Abstract

Immunotherapy with immunostimulatory antibodies has become a breakthrough therapeutic modality for solid tumours. However, only up to 50% of patients benefit and hence there is a renewed interest to vaccination to direct the immune attack against tumour antigens to widen the range of patients who benefit. Modern vaccine platforms such as viral-like particles have already demonstrated success in cancer prevention and the challenge is now to harness these approaches in patients with established malignancies. We have focused on a novel vaccine platform utilising a plant viral particle (PVP), which has been previously demonstrated that this single strand RNA (ssRNA) containing vaccine activated the immune mechanisms closely resembling the natural antiviral defence. Based on our previous mouse work, with sensing of viral RNA by plasmacytoid dendritic cells (pDCs), IFN-α was generated to activate conventional DCs (cDCs), and then prime Th1 immunity. We also confirmed that PVP with ssRNA packaged inside was capable to activate human DCs. The induction of anti-tumour antibody was another outcome. Subsequently, we explored this vaccine platform for induction of cellular responses against defined cancer targets. Initially using PVP loaded with a single model peptide, the induction of a rapid CD8 response of high magnitude was represented. In order to extend the application of this platform, the clinically relevant cancer testis antigens MAGEC1 and PASD1 were set as vaccine targets. In HLA-A2 transgenic (HHD) mouse model, PVP simultaneously targeting MAGEC1 and PASD1 induced CTLs, which were able to lyse human cancer cells expressing these antigens. We were accordingly keen to expend applicability to patient cohorts beyond HLA-A2+ patients, PVP loaded with whole protein antigens was subsequently tested. The vaccine induced CD8 and CD4 T-cell responses against epitopes delivered through the whole antigen were both detected. Of these, this flexible and economical platform can be adapted easily to deliver any antigenic peptides including multiple epitopes as well as whole proteins and may provide a universal platform for vaccination against cancer.

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