Engineered red blood cells as an off-the-shelf allogeneic anti-tumor therapeutic

Xuqing Zhang, Mengyao Luo, Shamael R. Dastagir, Mellissa Nixon, Annie Khamhoung, Andrea Schmidt, Albert Lee, Naren Subbiah, Douglas C. McLaughlin, Christopher L. Moore, Mary Gribble, Nicholas Bayhi, Viral Amin, Ryan Pepi, Sneha Pawar, Timothy J. Lyford, Vikram Soman, Jennifer Mellen, Christopher L. Carpenter, Laurence A. Turka, Thomas J. Wickham and Tiffany F. Chen ()
Additional contact information
Xuqing Zhang: Rubius Therapeutics, Inc.
Mengyao Luo: Rubius Therapeutics, Inc.
Shamael R. Dastagir: Rubius Therapeutics, Inc.
Mellissa Nixon: Rubius Therapeutics, Inc.
Annie Khamhoung: Rubius Therapeutics, Inc.
Andrea Schmidt: Rubius Therapeutics, Inc.
Albert Lee: Rubius Therapeutics, Inc.
Naren Subbiah: Rubius Therapeutics, Inc.
Douglas C. McLaughlin: Rubius Therapeutics, Inc.
Christopher L. Moore: Rubius Therapeutics, Inc.
Mary Gribble: Rubius Therapeutics, Inc.
Nicholas Bayhi: Rubius Therapeutics, Inc.
Viral Amin: Rubius Therapeutics, Inc.
Ryan Pepi: Rubius Therapeutics, Inc.
Sneha Pawar: Rubius Therapeutics, Inc.
Timothy J. Lyford: Rubius Therapeutics, Inc.
Vikram Soman: Rubius Therapeutics, Inc.
Jennifer Mellen: Rubius Therapeutics, Inc.
Christopher L. Carpenter: Rubius Therapeutics, Inc.
Laurence A. Turka: Rubius Therapeutics, Inc.
Thomas J. Wickham: Rubius Therapeutics, Inc.
Tiffany F. Chen: Rubius Therapeutics, Inc.

Nature Communications, 2021, vol. 12, issue 1, 1-14

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 E711-19, 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.

Date: 2021
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DOI: 10.1038/s41467-021-22898-3

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