102PTargeting human CD141+ DC using CLEC9A antibodies for cancer immunotherapy

Background: Dendritic cells (DC) are a heterogeneous cell population, with specialist subtypes driving specific immune responses. In mice, the cDC1 subset (also referred to as Batf3-dependent DC, XCR1⁺ DC, CD8⁺ DC in lymphoid tissues and CD103⁺ DC in peripheral tissues) is essential for the induction of tumour immune responses and for the efficacy of checkpoint inhibitor blockade and adoptive T cell immunotherapies. Vaccines that can deliver antigens (Ag) directly to DCs in vivo are more effective than cell-based therapies in mouse models and are promising approaches to translate to humans. CD141⁺ DC are the human cDC1 equivalent and specifically express the C-type lectin-like receptor CLEC9A, that facilitates cross-presentation of dead cell Ag. Targeting tumour-associated Ag (TAA) to human CD141⁺ DC using CLEC9A antibody (Ab) is therefore an attractive strategy to induce or boost tumour immune responses.

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