An engineered Accum‐E7 protein‐based vaccine with dual anti‐cervical cancer activity

• DOI: 10.1111/cas.16096
• Publication Date: 2024-01-30T05:40:09Z
• Authors: Jean‐Pierre Bikor...; Jamilah Abusarah; Marina Gonçalves; Roudy Farah; Wael Saad; Sebastien Talbot; Daniela Stanga; Simon Beaudoin; Sebastien Plouffe; Moutih Rafei
• Keywords: 0301 basic medicine; 03 medical and health sciences; ORIGINAL ARTICLES

Abstract Worldwide prevalence of cervical cancer decreased significantly with the use human papilloma virus (HPV)‐targeted prophylactic vaccines. However, these multivalent antiviral vaccines are inert against established tumors, which leave patients surgical ablative options possibly resulting in long‐term reproductive complications and morbidity. In an attempt to bypass this unmet medical need, we designed a new E7 protein‐based vaccine formulation using Accum™, technology platform promote endosome‐to‐cytosol escape as means enhance protein accumulation target cells. Prophylactic vaccination immunocompetent mice Accum‐E7 (aE7) leads complete protection from despite multiple challenges conducted ascending C3.43 cellular doses (0.5‐, 1.0‐, 2.0 × 10 6 cells). Moreover, humoral response induced by aE7 was higher magnitude compared naked displayed potent inhibitory effects on proliferation vitro. When administered therapeutically animals pre‐established or Tal3 vaccine‐induced synergized immune checkpoint blockers (anti‐PD‐1, anti‐CTLA4, anti‐CD47) effectively control tumor growth. Mechanistically, observed therapeutic effect requires cross‐presenting dendritic cells well CD8 T predominantly, non‐negligible role played both CD4 + CD19 lymphocytes. good laboratory practice (GLP) studies revealed that is immunogenic tolerated no adverse fourfold exceeding dose. nutshell, represents ideal candidate for further clinical development it uses single engineered capable exhibiting activity.