Human CLEC9A antibodies deliver NY-ESO-1 antigen to CD141 dendritic cells to activate naïve and memory NY-ESO-1-specific CD8 T cells.
Kelly-Anne Masterman, Oscar L Haigh, Kirsteen M Tullett, Ingrid M Leal-Rojas, Carina Walpole, Frances E Pearson, Jonathon Cebon, Christopher Schmidt, Liam O'Brien, Nikita Rosendahl, Ghazal Daraj, Irina Caminschi, Eric H Gschweng, Roger P Hollis, Donald B Kohn, Mireille H Lahoud, Kristen J Radford
Journal for ImmunoTherapy of Cancer | Published : 2020
BACKGROUND: Dendritic cells (DCs) are crucial for the efficacy of cancer vaccines, but current vaccines do not harness the key cDC1 subtype required for effective CD8+ T-cell-mediated tumor immune responses. Vaccine immunogenicity could be enhanced by specific delivery of immunogenic tumor antigens to CD141+ DCs, the human cDC1 equivalent. CD141+ DCs exclusively express the C-type-lectin-like receptor CLEC9A, which is important for the regulation of CD8+ T cell responses. This study developed a new vaccine that harnesses a human anti-CLEC9A antibody to specifically deliver the immunogenic tumor antigen, NY-ESO-1 (New York esophageal squamous cell carcinoma 1), to human CD141+ DCs. The abilit..View full abstract