SL-172154 (SIRPα-Fc-CD40L) is currently in a Phase 1 clinical trial in subjects with ovarian cancer.
SL-172154 is a bi-functional fusion protein that targets CD47 on malignant cells and CD40 on immune cells (antigen presenting cells).
The ARC consists of Sirpα linked to CD40L, providing checkpoint blockade (CD47 axis) and potent costimulation (CD40 axis). CD47 is upregulated in essentially every cancer type to inhibit innate immune cells from phagocytosing (eating) the tumor cells. By blocking this signal though Sirpα binding, the surface of the tumor cells are coated with the ARC, allowing the CD40L side to bind to CD40 on antigen presenting cells (APCs), which will lead to enhanced antigen presentation to CD8+ and CD4+ T lymphocytes and tumor cell phagocytosis by the APC cell.