Abstract 1475: Microbiome derived peptides stimulate strong immune response against tumor associated antigens and trigger in vivo tumor regression after vaccination
Authors: Laurent Chene, Caroline Diveu Sader, Joao Magalhaes, Francesco Strozzi, Lorenzo Tibaldi, Celia Mendez, Simon Baeriswyl, Arnaud Laveissiere, Christophe Bonny
Journal: Cancer Research (2019)

Abstract Peptide-based vaccination is an immunotherapeutic approach for the treatment of cancer that aims to deliver immunogenic peptides corresponding to specific tumor associated antigens to patients. Despite promising pre-clinical results in animal models, most cancer vaccination approach has not demonstrated unequivocal efficacy in patients. The ability of a peptide cancer vaccine to generate a strong immune response depends on several factors including the avidity of the peptide for the MHC complexes, the capacity of the antigen to be recognized by the immune system as self or non-self and the existence of T cell clones (naïve or memory) that are able to recognize those peptides. Gut colonization is one of the factor that drive the development of T cells and the presence of commensal specific memory T-cell is well reported in the literature and is now currently admitted. Several evidences support that these T cells can be re-activated and can migrate to inflammatory sites where the antigen is expressed. We have developed an innovative, microbiome-based approach for the development of therapeutic peptide cancer vaccines base. Our approach is based on the notion of molecular mimicry, by which a microbial derived peptide vaccine holding molecular similarity with a tumor-associated epitope would trigger a tumor-specific cytotoxic T cell immune response. By developing a dedicated in silico pipeline, we were able to identify bacterial antigens that could elicit strong immune response in WT mice. Furthermore, these bacterial antigens could be selected to generate T cell reactivity against self-peptides that are by themselves not immunogenic. The same pipeline was used to identify bacterial antigens able to bind human HLA-A2 and displaying molecular mimicry with selected tumor associated antigens. While HLA-A2 transgenic mice vaccination with tumor associated antigens doesn’t lead to immunization, vaccination with bacterial antigens results in a strong immune response against both bacterial peptides and selected tumor associated antigens. Furthermore, adoptive transfer of T cell from mice immunized with bacterial peptides into tumor engrafted nude mice leads to tumor control in the presence of Check Point Inhibitors. A first vaccine candidate targeting three different tumor drivers overexpressed in Glioblastoma and other solid tumors will enter the clinic this year. Citation Format: Laurent Chene, Caroline Diveu Sader, Joao Magalhaes, Francesco Strozzi, Lorenzo Tibaldi, Celia Mendez, Simon Baeriswyl, Arnaud Laveissiere, Christophe Bonny. Microbiome derived peptides stimulate strong immune response against tumor associated antigens and trigger in vivo tumor regression after vaccination [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1475.