Modified Extracorporeal Photopheresis As An Immunotherapy In Murine Melanoma

Abstract

Extracorporeal Photochemotherapy (ECP) is a widely used immunotherapy for cutaneous T cell lymphoma, as well as an immunomodulatory treatment for graft versus host disease (GVHD) and rejection of allografts. We hypothesized that ECP’s physiologic induction of large-scale monocyte-to-dendritic antigen presenting cell (APC) conversion is mechanistically responsible for both its anti-cancer effect and its tolerogenic impact in the transplant setting. To interrogate this possibility in an experimental system, we developed an ECP device that is scalable from mouse to man and tested its capacity to produce APCs that, when advantageously tuned and tumor antigen-loaded, can limit the growth of otherwise lethal tumors in the engineered Yale University Mouse Melanoma (YUMM) 1.7 model (driven by PTEN loss, BRAFV600E activation and CDKN2A mutations). Untreated control mouse tumors (N=169) were 7 to 10-fold (

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