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Targeting self and neo-epitopes with a modular self-adjuvanting cancer vaccine.

  • Belnoue E AMAL Therapeutics, Geneva, Switzerland.
  • Mayol JF AMAL Therapeutics, Geneva, Switzerland.
  • Carboni S AMAL Therapeutics, Geneva, Switzerland.
  • Di Berardino Besson W AMAL Therapeutics, Geneva, Switzerland.
  • Dupuychaffray E AMAL Therapeutics, Geneva, Switzerland.
  • Nelde A University of Tübingen, Interfaculty Institute for Cell Biology, Department of Immunology, Tubingen, Germany.
  • Stevanovic S University of Tübingen, Interfaculty Institute for Cell Biology, Department of Immunology, Tubingen, Germany.
  • Santiago-Raber ML AMAL Therapeutics, Geneva, Switzerland.
  • Walker PR Centre for Translational Research in Onco-Hematology, Department of Internal Medicine Specialties, University of Geneva and Division of Oncology, Geneva University Hospitals, Geneva, Switzerland.
  • Derouazi M AMAL Therapeutics, Geneva, Switzerland.
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  • 2019-04-24
Published in:
  • 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
English 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.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/232834
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