Oncolytic adenovirus ORCA-010 increases the type-1 T cell stimulatory capacity of melanoma-conditioned dendritic cells.

Oncolytic adenovirus ORCA-010 increases the type-1 T cell stimulatory capacity of melanoma-conditioned dendritic cells. Clin Exp Immunol. 2020 Apr 17;: Authors: López González M, van de Ven R, de Haan H, van Eck van der Sluijs J, Dong W, van Beusechem VW, de Gruijl TD Abstract Immune checkpoint blockade has resulted in durable responses in patients with metastatic melanoma, but only in a fraction of treated patients. For immune checkpoint inhibitors (ICI) to be effective, sufficient infiltration with tumor-reactive T cells is essential. Oncolytic viruses (OV) selectively replicate in and lyse tumor cells and so induce an immunogenic form of cell death, providing at once a source of tumor-associated (neo)antigens and of danger signals that together induce effective T cell immunity and tumor infiltration. Melanoma-associated suppression of dendritic cell (DC) differentiation effectively hampers OV- or immune checkpoint inhibitor (ICI)-induced antitumor immunity, due to a consequent inability to prime and attract antitumor effector T cells. Here, we set out to study the effect of ORCA-010, a clinical stage oncolytic adenovirus, on DC differentiation and functionality in the context of human melanoma. In melanoma and monocyte co-cultures, employing a panel of five melanoma cell lines with varying origins and oncogenic mutation status, we observed clear suppression of DC development with apparent skewing of monocyte differentiation to a...
Source: Clinical and Developmental Immunology - Category: Allergy & Immunology Authors: Tags: Clin Exp Immunol Source Type: research