Engineered red blood cells as an off-the-shelf allogeneic anti-tumor therapeutic
Xuqing Zhang, Mengyao Luo, Shamael R. Dastagir, Mellissa J. Nixon, Annie Khamhoung, Andrea Schmidt, Albert Lee, Naren Subbiah, Douglas C. McLaughlin, Christopher Moore, Mary Gribble, Nicholas L Bayhi, Viral Amin, Ryan Pepi, Sneha Pawar, Timothy J. Lyford, Vikram Soman, Jennifer Mellen, Christopher L. Carpenter, Laurence A. Turka, Thomas J. Wickham, Tiffany F. Chen
Abstract
Abstract Checkpoint inhibitors and T-cell therapies have highlighted the critical role of T cells in anti-cancer immunity. However, limitations associated with these treatments drive the need for alternative approaches. Here, we engineer red blood cells into artificial antigen-presenting cells (aAPCs) presenting a peptide bound to the major histocompatibility complex I, the costimulatory ligand 4-1BBL, and interleukin (IL)-12. This leads to robust, antigen-specific T-cell expansion, memory formation, additional immune activation, tumor control, and antigen spreading in tumor models in vivo. The presence of 4-1BBL and IL-12 induces minimal toxicities due to restriction to the vasculature and spleen. The allogeneic aAPC, RTX-321, comprised of human leukocyte antigen-A*02:01 presenting the human papilloma virus (HPV) peptide HPV16 E7 11-19 , 4-1BBL, and IL-12 on the surface, activates HPV-specific T cells and promotes effector function in vitro. Thus, RTX-321 is a potential ‘off-the-shelf’ in vivo cellular immunotherapy for treating HPV + cancers, including cervical and head/neck cancers.