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Novel Blood Therapeutics

Sponsor: Scientific Committee on Transfusion Medicine
Program: Scientific Program
Hematology Disease Topics & Pathways:
antibodies, Biological, Combinations, Therapies
Saturday, December 5, 2020: 9:25 AM-9:30 AM

Description:
While red blood cells (RBCs) play a critical role in the transport and delivery of oxygen to tissue, new research demonstrates that they can be engineered into cargo RBCs that can be used to deliver drugs throughout the body, track red blood cells, visualize blood vessels, or induce immune tolerance to specific antigenic peptides.  Additionally, searches for non-cardiotoxic artificial blood substitutes continue to alleviate blood availability concerns and side effects such as alloimmunization. This session will present cutting-edge advancements in the development and potential benefits of RBC-based therapeutics and novel hemoglobin-based oxygen carriers.

Dr. Vladimir Muzykantov will discuss how red blood cells (RBCs) can be used to deliver dugs.  RBCs are ideal natural carriers for diverse therapeutic, prophylactic and diagnostic (imaging) agents. Strategies to load these agents into RBCs include encapsulation into isolated RBC via transient pores in cell membrane, genetic modification of RBC precursors, and coupling to RBC surface. Dr. Muzykantov’s talk will focus on the latter approach, whereby a single injection of compounds targeted to RBC surface determinants can uniquely "paint" circulating RBCs in animal studies enabling enhanced pharmacokinetics and unusual distribution of the compound cargoes in the body.

Dr. Hidde Ploegh will discuss how the immune system can be retrained to ignore the antigens that usually trigger inappropriate immune responses in autoimmune diseases such as multiple sclerosis and type 1 diabetes using mouse models.  Autoimmune diseases are characterized by inappropriate immune responses in which the body destroys its own cells. Dr. Ploegh will discuss how cargo red blood cells (RBCs) loaded with antigenic peptides,  can be used to redirect the immune system and allow these antigens that usually cause an inappropriate immune response to be tolerated - a method called tolerance induction.

Dr. Leticia Hosta-Rigau will discuss the development of hemoglobin-loaded nanoparticles (Hb-NPs) as a novel type of advanced hemoglobin-based oxygen carriers (HBOCs). She will discuss how Hb-NPs aim at addressing major challenges in the field of blood surrogates such as attaining a high Hb loading and long circulation times. Antioxidant coatings are incorporated into the Hb-NPs in order to minimize the conversion of Hb into nonfunctional methemoglobin. Decoration with PEG results in decreased protein adsorption onto the Hb-NPs surface, suggesting a prolonged retention time within the body. Dr. Hosta-Rigau will also discuss how the Hb-NPs preserve the reversible oxygen-binding and releasing properties of Hb.

Co-chairs:
Simone A. Glynn, MD, MPH, National Heart, Lung and Blood Institute and Stella P Chou, MD, Children's Hospital of Philadelphia
Disclosures:
No relevant conflicts of interest to declare.
While red blood cells (RBCs) play a critical role in the transport and delivery of oxygen to tissue, new research demonstrates that they can be engineered into cargo RBCs that can be used to deliver drugs throughout the body, track red blood cells, visualize blood vessels, or induce immune tolerance to specific antigenic peptides.  Additionally, searches for non-cardiotoxic artificial blood substitutes continue to alleviate blood availability concerns and side effects such as alloimmunization. This session will present cutting-edge advancements in the development and potential benefits of RBC-based therapeutics and novel hemoglobin-based oxygen carriers.

Dr. Vladimir Muzykantov will discuss how red blood cells (RBCs) can be used to deliver dugs.  RBCs are ideal natural carriers for diverse therapeutic, prophylactic and diagnostic (imaging) agents. Strategies to load these agents into RBCs include encapsulation into isolated RBC via transient pores in cell membrane, genetic modification of RBC precursors, and coupling to RBC surface. Dr. Muzykantov’s talk will focus on the latter approach, whereby a single injection of compounds targeted to RBC surface determinants can uniquely "paint" circulating RBCs in animal studies enabling enhanced pharmacokinetics and unusual distribution of the compound cargoes in the body.

Dr. Hidde Ploegh will discuss how the immune system can be retrained to ignore the antigens that usually trigger inappropriate immune responses in autoimmune diseases such as multiple sclerosis and type 1 diabetes using mouse models.  Autoimmune diseases are characterized by inappropriate immune responses in which the body destroys its own cells. Dr. Ploegh will discuss how cargo red blood cells (RBCs) loaded with antigenic peptides,  can be used to redirect the immune system and allow these antigens that usually cause an inappropriate immune response to be tolerated - a method called tolerance induction.

Dr. Leticia Hosta-Rigau will discuss the development of hemoglobin-loaded nanoparticles (Hb-NPs) as a novel type of advanced hemoglobin-based oxygen carriers (HBOCs). She will discuss how Hb-NPs aim at addressing major challenges in the field of blood surrogates such as attaining a high Hb loading and long circulation times. Antioxidant coatings are incorporated into the Hb-NPs in order to minimize the conversion of Hb into nonfunctional methemoglobin. Decoration with PEG results in decreased protein adsorption onto the Hb-NPs surface, suggesting a prolonged retention time within the body. Dr. Hosta-Rigau will also discuss how the Hb-NPs preserve the reversible oxygen-binding and releasing properties of Hb.

Vladimir Muzykantov, PhD

Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

Hidde L. Ploegh, PhD

Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA

Leticia Hosta-Rigau, PhD

Technical University of Denmark, Kongens Lyngby, Hovedstaden, Denmark

See more of: Scientific Program