612 Human CLEC9A antibodies deliver NY-ESO-1 antigen to CD141+ dendritic cells to activate naïve and memory NY-ESO-1-specific CD8+ T cells

• DOI: 10.1136/jitc-2020-sitc2020.0612
• Publication Date: 2020-11-09T19:17:02Z
• Authors: Kelly-Anne Masterman; Oscar Haigh; Kirsteen Tullett; Ingrid Leal-Rojas; Carina Walpole; Frances Pearson; Jonathon Cebon; Christopher Schmidt; Liam O’Brien; Nikita Rosendahl; Ghazal Daraj; Irina Caminschi; Eric Gschweng; Roger Hollis; Donald Kohn; Mireille Lahoud; Kristen Radford; Kristen Radford
• Keywords: Tumor Antigen

<h3>Background</h3> Dendritic cells (DC) are crucial for the efficacy of cancer vaccines, but current vaccines do not harness key cDC1 subtype required effective CD8+ T cell mediated tumor immune responses. Vaccine immunogenicity could be enhanced by specific delivery immunogenic antigens to CD141+ DC, human equivalent. DC exclusively express C-type-lectin-like receptor CLEC9A, which is important regulation This study developed a new vaccine that harnesses anti-CLEC9A antibody specifically deliver antigen, NY-ESO-1 DC. The ability CLEC9A-NY-ESO-1 activate naïve and memory was examined compared comprised DEC-205-NY-ESO-1 targets all <h3>Methods</h3> Human anti-CLEC9A, anti-DEC-205 isotype control IgG4 antibodies were genetically fused polypeptide. Cross-presentation NY-ESO-1- epitope reactivity responses in melanoma patients assessed IFNγ production following incubation patient peripheral blood mononuclear with targeting antibodies. Humanized mice containing subsets repertoire NY-ESO-1-specific used investigate priming. effector function measured expression IFNγ, MIP-1β, TNF CD107a lysis target cells. <h3>Results</h3> Ab at mediating cross-presentation multiple epitopes activation When benchmarked conjugated an untargeted or anti-human DEC-205, superior ex vivo reactivation patients. Moreover, induced priming polyclonal potent killing capacity vitro. <h3>Conclusions</h3> These data advocate as attractive strategy enhance tumour NY-ESO-1-expressing malignancies. <h3>Ethics Approval</h3> Written informed consent obtained sample acquisition line standards established Declaration Helsinki. Study approval granted Mater Research Ethics Committee (HREC13/MHS/83 HREC13/MHS/86) U.S. Army Medical Materiel Command (USAMRMC) Office Protections, Protection (HRPO; A-18738.1, A-18738.2, A-18738.3). All animal experiments approved University Queensland Animal conducted accordance Australian Code Care Use Animals Scientific Purposes addition laws United States regulations Department Agriculture.