Definition

An off-the-shelf (OTS) preparation of allogeneic red blood cells (RBCs) genetically engineered with a lentiviral vector to express on the cell surface 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 4-1BBL/IL-12 RTX-224, 4-1BBL and IL-12 expressed on these cells bind to 4-1BB and IL-12 receptors. This induces the proliferation and activation of CD4- and CD8-positive T cells and natural killer (NK) cells, which induces the production of inflammatory cytokines and chemokines, and leads to the activation of antigen-presenting cells (APCs) and enhanced antigen presentation. Altogether, this activates both the adaptive and innate immune system and leads to the induction of anti-tumor immune responses, thereby killing the tumor cells. 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.