engineered red blood cells expressing HPV16 E7/4-1BBL/IL-12 RTX-321

A preparation of allogeneic red blood cells (RBCs) engineered to act as artificial antigen presenting cells (aAPCs) and express on the cell surface the human papillomavirus (HPV) type 16 E7 protein on the major histocompatibility complex (MHC) I, the co-stimulatory molecule tumor necrosis factor ligand superfamily (TNFSF) member 9 (TNFSF9; 4-1BBL) and the immunostimulatory cytokine interleukin-12 (IL-12), with potential immunomodulating and antineoplastic activities. Upon administration of the engineered RBCs expressing HPV16 E7/4-1BBL/IL-12 RTX-321, these cells activate the immune system to mount a cytotoxic T-lymphocyte (CTL) immune response against tumor cells expressing HPV16 E7. In addition, 4-1BBL and IL-12 expressed on these cells bind to 4-1BB and IL-12 receptors 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 further induces an anti-tumor immune response. HPV16 E7 plays an important role in the development of certain types of cancer. 4-1BB, a surface glycoprotein of the tumor necrosis factor receptor superfamily (TNFRSF), is an inducible costimulatory receptor that plays a key role in T-cell proliferation, survival and cytolytic activity. IL-12 promotes the activation of NK cells, which induces both the secretion of IFN-g and a CTL response against the tumor cells.