engineered red blood cells coexpressing 4-1BBL and IL-15TP RTX-240

A preparation of allogeneic, off-the-shelf (OTS) red blood cells (RBCs) engineered to express both the co-stimulatory molecule tumor necrosis factor ligand superfamily (TNFSF) member 9 (TNFSF9; 4-1BBL) and a fusion protein composed of the trans-presented cytokine interleukin (IL)-15/IL-15-receptor alpha (IL-15Ra) (IL-15TP) with potential modulating and antineoplastic activities. CD34+ hematopoietic precursor cells (HPC) are collected by apheresis from a healthy O negative donor, purified, and engineered with a lentiviral vector to express 4-1BBL and IL-15TP. The cells are then further expanded and differentiated until the nucleus is ejected, resulting in a mature reticulocyte. Upon administration of the engineered red blood cells co-expressing 4-1BBL and IL-15TP RTX-240, the RBCs express both 4-1BBL and IL-15TP on their cell surfaces. 4-1BBL and IL-15TP bind to and subsequently induce the proliferation and activation of natural killer (NK) cells and T cells. This enhances the secretion of cytokine interferon-gamma (IFN-g) and results in the induction of an anti-tumor immune response.