Résumés
Résumé
La mise en évidence de séquences immunostimulantes au sein des brins d’ADN en dehors de toute traduction est une découverte récente de la biologie de l’ADN. La présence de motifs CpG, reconnus par un récepteur spécifique (Toll-like receptor 9), induit l’activation des macrophages, des cellules natural killer (NK) et des lymphocytes B, et oriente la réponse lymphocytaire T vers le profil Th1. Les propriétés immunostimulantes des motifs CpG ont été utilisées avec succès dans de nombreux modèles animaux de vaccins, d’allergies ou de maladies infectieuses, et plusieurs essais cliniques sont en cours. Dans le cas des cancers, lorsqu’un antigène tumoral est connu, les motifs CpG peuvent être utilisés comme adjuvants dans un cadre vaccinal, ou combinés avec des anticorps monoclonaux. Dans les autres cas, des oligonucléotides de synthèse portant des motifs CpG (CpG-ODN) peuvent être utilisés de façon locale pour stimuler l’immunité innée et favoriser l’émergence d’une réponse immune spécifique. Cet article fait le point sur les progrès récents dans l’utilisation des CpG-ODN en cancérologie.
Summary
Bacterial DNA and synthetic oligodeoxynucléotides containing CpG motifs (CpG-ODN) are the ligands for the Toll-like receptor 9 (TLR9), which is expressed by B-lymphocytes and a subset of dendritic cells. CpG-ODN are strong activators of both innate and specific immunity, and drive the immune response towards the Th1 phenotype. Given the promising results obtained in several experimental models of allergies or infections, CpG-ODN are now entering clinical trials for these diseases. In cancer, promising approaches combined CpG-ODN with tumor antigens, monoclonal antibodies or dendritic cells. When no relevant tumor antigen is known, CpG-ODN can be used alone to activate locally the innate immunity and trigger a tumor-specific immune response, overcoming the need for the identification of a tumoral antigen. Preclinical models have shown impressive results and several clinical trials are on-going worldwide in melanoma, lymphoma, renal carcinoma, breast cancer and glioblastoma.
Parties annexes
Références
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