Combination vaccine based on citrullinated vimentin and enolase peptides induces potent CD4-mediated anti-tumor responses

• DOI: 10.1136/jitc-2020-000560
• Publication Date: 2020-06-19T09:35:27Z
• Authors: Victoria A Brentv...; Rachael L Metheri...; Ian Daniels; Suha Atabani; Peter Symonds; Katherine W Cook; Mireille Vankemme...; Ruhul Choudhury; Poonam Vaghela; Mohamed Gijon; Ghislaine Meiners; Willem-Jan Krebber; Cornelis J M Melief; Lindy G Durrant
• Keywords: Enolase

Stress-induced post-translational modifications occur during autophagy and can result in generation of new epitopes immune recognition. One such modification is the conversion arginine to citrulline by peptidylarginine deiminase enzymes.We used Human leukocyte antigen (HLA) transgenic mouse models assess immunogenicity citrullinated peptide vaccine cytokine Enzyme linked immunosorbant spot (ELISpot) assay. Vaccine efficacy was assessed tumor therapy studies using HLA-matched B16 melanoma ID8 ovarian expressing either constitutive or interferon-gamma (IFNγ) inducible Major Histocompatibility Complex (MHC) class II (MHC-II) as represented most human tumors. To determine importance CD4 T cells therapy, we analyzed cell infiltrate into murine tumors flow cytometry performed presence CD8 depletion. We repertoire peptides cancer patients healthy donors cytometry.The combination vimentin enolase (Modi-1) stimulated strong responses mice. Responses resulted a potent anti-tumor against established generated immunological memory which protected rechallenge. Depletion CD4, but not cells, abrogated primary response well This further reinforced successful regression being associated with an increase tumor-infiltrating reduction tumor-associated myeloid suppressor cells. The also relied on direct recognition only MHC-II were rejected. A comparison different Toll-like receptor (TLR)-stimulating adjuvants showed that Modi-1 induced Th1 when combined granulocyte-macrophage colony-stimulating factor (GMCSF), TLR9/TLR4, TLR9, TLR3, TLR1/2 TLR7 agonists. Direct linkage agonist allowed dose be reduced 10-fold 100-fold without loss activity. Furthermore, seen patients.Modi-1 induces CD4-mediated present suggesting could effective for patients.