Human CLEC9A antibodies deliver NY-ESO-1 antigen to CD141+ dendritic cells to activate naïve and memory NY-ESO-1-specific CD8+ T cells
Abstract
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 ability of the CLEC9A-NY-ESO-1 antibody to activate NY-ESO-1-specific naïve and memory CD8+ T cells was examined and compared with a vaccine comprised of a human DEC-205-NY-ESO-1 antibody that targets all human DCs.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 01, 2020
- Source ID
- 10.1136/jitc-2020-000691
Entities
People
- Carina Walpole
- Christopher Schmidt
- Donald B. Kohn
- Eric H Gschweng
- Frances E Pearson
- Ghazal Daraj
- Ingrid M Leal-rojas
- Irina Caminschi
- Jonathon Cebon
- Kelly-anne Masterman
- Kirsteen M Tullett
- Kristen J Radford
- Liam O'brien
- Mireille H Lahoud
- Nikita Rosendahl
- Oscar L. Haigh
- Roger P Hollis
Organizations
- Mater Foundation
- National Health and Medical Research Council
- United States Department of Defense
- Worldwide Cancer Research