Belnoue E Mayol JF Carboni S Di Berardino Besson W Dupuychaffray E Nelde A Stevanovic S Santiago-Raber ML Walker PR Derouazi M 2019 Induction of a potent CD4 and CD8 T-cell response against tumor-specific and tumor-associated antigen is critical for eliminating tumor cells. Recent vaccination strategies have been hampered by an inefficacious and low amplitude immune response. Here we describe a self-adjuvanted chimeric protein vaccine platform to address these challenges, characterized by a multidomain construction incorporating (i) a cell penetrating peptide (CPP) allowing internalization of several multiantigenic Major Histocompatibility Complex (MHC)-restricted peptides within (ii) the multiantigenic domain (Mad) and (iii) a TLR2/4 agonist domain (TLRag). Functionality of the resulting chimeric protein is based on the combined effect of the above-mentioned three different domains for simultaneous activation of antigen presenting cells and antigen cross-presentation, leading to an efficacious multiantigenic and multiallelic cellular immune response. Helper and cytotoxic T-cell responses were observed against model-, neo- and self-antigens, and were highly potent in several murine tumor models. The safety and the immunogenicity of a human vaccine candidate designed for colorectal cancer treatment was demonstrated in a non-human primate model. This newly engineered therapeutic vaccine approach is promising for the treatment of poorly infiltrated tumors that do not respond to currently marketed immunotherapies. application/pdf https://sonar.ch/global/documents/232834 eng info:eu-repo/semantics/altIdentifier/doi/10.1172/jci.insight.127305 info:eu-repo/semantics/altIdentifier/pmid/31013258 info:eu-repo/semantics/openAccess JCI insight. - 2019 Cellular immune response Colorectal cancer Immunotherapy Oncology Vaccines Adjuvants, Immunologic Animals Antigen Presentation Antigens, Neoplasm CD4-Positive T-Lymphocytes CD8-Positive T-Lymphocytes Cancer Vaccines Cell-Penetrating Peptides Colorectal Neoplasms Dendritic Cells HEK293 Cells Histocompatibility Antigens Class II Humans Immunity, Cellular Immunologic Memory Lymphocytes, Tumor-Infiltrating Macaca fascicularis Major Histocompatibility Complex Mice T-Lymphocytes, Cytotoxic T-Lymphocytes, Helper-Inducer Toll-Like Receptor 2 Toll-Like Receptor 4 Toll-Like Receptors Targeting self and neo-epitopes with a modular self-adjuvanting cancer vaccine. http://purl.org/coar/resource_type/c_6501