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Novel Blood Therapeutics: The Versatility of RBCs and the Molecules That May Replace Them

December 4, 2020

Dr. Hosta-Rigau presents her talk on synthetic red cells.

More than three centuries ago, microscopist Antoni van Leeuwenhoek was the first to draw an illustration of “red corpuscles,” the cells we know now as red blood cells (RBCs). RBCs are known to function as key oxygen carriers, and the criticality of this cell type is seen firsthand by hematologists and transfusion medicine physicians when they encounter patients with anemia. The Scientific Program session on Novel Blood Therapeutics (live Q&A Saturday, December 5, at 9:30 a.m. Pacific time), chaired by Drs. Stella Chou and Simone Glynn, discusses cutting-edge research that exploits RBCs to perform functions that we do not normally associate with these cells, such as drug delivery and immune tolerance, as well as research on the development of “blood substitutes.” Dr. Chou commented, “While making red cells in vitro for transfusion is currently hampered by the 2 trillion cells needed per unit, the work presented in this session shows the use of red cells for novel therapeutics, and an alternative for red cells for select patient populations. In vitro–derived ‘universal’ red cells can potentially replace donor red cells for these novel therapeutic indications.”

Drug delivery systems are technologies engineered for the targeted delivery of therapeutic agents. With the need to deliver drugs more precisely to specific sites over periods of time, the field is rapidly exploring novel ways to deliver medications safely and effectively. Rapid expansion of knowledge in efficient drug delivery, such as transport in the circulatory system and drug movement through cells and tissues, have contributed to the development of new modes of drug delivery. In this context, Dr. Vladimir Muzykantov discusses the innovative use of RBCs to deliver drugs for both diagnostic and therapeutic indications. In the diagnostic arena, Dr. Muzykantov explores the use of RBC-loaded agents for diagnostic imaging — a key modality used to examine presence and extent of disease. Several strategies used to manipulate RBCs to carry drugs are discussed including introduction through pores on the cell surface, genetic modifications of RBC precursors, and coupling the agent to the RBC. The latter strategy results in “painting” the RBC and offers certain pharmacokinetic advantages that can be exploited. Personally, I am really excited for this talk to help me realize that this is not all in the realm of science fiction!

Horror autotoxicus (literally, “the horror of self-toxicity”) is a term coined by the immunologist Paul Ehrlich to describe the body’s innate aversion to immunological self-destruction. With time, however, it became well accepted that autoimmune responses are commonly seen in vertebrates. Autoimmunity refers to a condition where the individual’s immune system mounts an inappropriate immune response against their own cells; millions of people live with these conditions, many of which carry high morbidity and mortality. While there has been progress with the use of biologics for the treatment of some of these conditions, many others have few or no drugs or are refractory to standard therapies. Dr. Hidde Ploegh discusses how the immune system can be retrained to ignore the antigens that usually trigger inappropriate immune responses in autoimmune diseases. The speaker details the pathophysiology of autoimmune diseases such as multiple sclerosis and type 1 diabetes using mouse models generated to study them. In this context, Dr. Ploegh also discusses a key concept called “tolerance”, which refers to the prevention of an immune response against a particular antigen. This session also covers the exciting concept of using RBCs to carry antigenic peptide “cargo” to redirect the immune system and allow these same antigens that cause a deleterious immune reaction to be “tolerated.”

Transfusion of RBCs obtained from normal blood donors is lifesaving for patients with a variety of medical and surgical conditions. In fact, more than 10 million units of RBCs are transfused every year in the United States alone. RBC transfusion carries several risks including risk of alloimmunization to RBC antigens, transfusion reactions, and infectious complications. Additionally, blood shortages are becoming increasingly common due to various reasons, and recent crises such as infectious pandemics and periods of civil unrest have further exacerbated the situation. In this backdrop, there is a high level of interest in the development of hemoglobin-based oxygen carriers (HBOCs) as a substitute for donor-derived blood. Dr. Leticia Hosta-Rigau covers the exciting developments and research around hemoglobin-loaded nanoparticles as a novel type of HBOC. Key challenges that need to be surmounted to enable development of efficacious HBOCs include high loading of the HBOC with oxygen and sufficiently long circulation times. Additionally, an effective HBOC should be able to support, like hemoglobin does, reversible oxygen-binding and release. This session should be of interest to physicians, advanced practice providers, and scientists with translational/clinical research interests in transfusion medicine and hematology.

Dr. Padmanabhan indicated no relevant conflicts of interest.

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