Special Scientific Symposia

Cellular Heterogeneity and Relationship to Clinical Outcomes

Sunday, December 8, 2024, 4:30 p.m. - 5:45 p.m.
San Diego Convention Center, Room 33

Cellular therapies are by nature heterogeneous, but regulatory and industry groups have focused on defining products with "critical product attributes" while minimizing heterogeneity or discounting the challenges of obtaining homogenous populations of cells. Understanding the potential risks and benefits of cellular heterogeneity, in both post-transplant and immune effector cell populations, is important information for cell therapy practitioners and researchers alike. In this session, we will hear from speakers with expertise in studying both natural and purposefully designed heterogeneous cellular products and will consider the benefits and technical challenges of obtaining purely homogenous populations of cells.

Dr. Good will present research on factors correlating with response and toxicity outcomes in chimeric antigen receptor (CAR) T cell treatment of large B cell lymphoma (LBCL). In particular, she will discuss the heterogeneity of CAR T cells, focusing on the impact of CAR T regulatory cells (Treg) on efficacy and neurotoxicity. Additionally, Dr. Good will share unpublished findings on T cell intrinsic factors affecting CAR T cell expansion, persistence, and tumor homing, results obtained from lineage tracing studies using endogenous T cell receptor sequences.

As screening tools have improved, we are now able to simultaneously query the entire genome to rapidly pinpoint key genetic nodes that govern human T cell behaviors. Dr. Carnevale will share studies using these screening tools to pressure test T cell therapies and identify loss- and gain-of-function gene targets that can be used to steer T cells into desired therapeutic behaviors. Specifically, she will cover lessons learned and steps being taken to successfully harness pooled screening approaches in T cells. She will also describe how these efforts might be translated to a clinical future where engineered pools of T cell products are created based on a variety of unique gene edits in CD4 and CD8 T cells.

Treg maintain immune homeostasis and are a promising cell therapy to induce transplantation tolerance. Dr. Levings will discuss the challenges to the wider applicability of Treg therapy, including a difficulty in obtaining large numbers of homogeneous cells and the technical ability to maximize the potency of the finalized product. In particular, work towards the scale up and clinical testing of an allogeneic “off the shelf” Treg product, as well as the use of chimeric antigen receptor engineering to maximize Treg potency and tolerance induction, will be discussed.

Chair:

Craig Byersdorfer, MD
University of Pittsburgh
Pittsburgh, PA

Speakers:

Zinaida Good, PhD
Stanford University School of Medicine
Stanford, CA
Heterogeneity of CD19 CAR T Cells

Julia Carnevale, MD
University of California San Francisco
San Francisco, CA
Purposeful Heterogeneity of CAR T Cells

Megan Levings
University of British Columbia, Canada
Vancouver, BC, CAN
Heterogeneity of Cells in Transplantation

Interface of Complement and Coagulation

Saturday, December 7, 2024, 4:00 p.m. - 5:15 p.m.
San Diego Convention Center, Room 33

The complement system and coagulation pathways are the main pillars of immunity and hemostasis respectively that undergo significant activation with injury. While appearing distinct, it is recognized that significant crosstalk exists between the two systems and recently established molecular mechanisms provide insights into a wide variety of disorders. This session will focus on new molecular links identified in complement activation in specific and highly relevant clinical disorders.

Chair:

David Kavanagh
New Castle University
Newcastle Upon Tyne, United Kingdom

Speakers:

David Kavanagh
New Castle University
Newcastle Upon Tyne, United Kingdom
Complement and the Prothrombotic State

Efthymia Vlachaki, Consultant Hematologist
Hippokrateon Hospital
Thessaloniki, Greece
Complement Activation and Preclampsia

Lubka T Roumenina, PhD
INSERM UMRS1138 Cordeliers Research Center
Paris, France
Sickle Cell Disease and Complement Activation

Interrogating the Impact of the Intestinal Microbiome on Transplant and Cellular Therapies

Sunday, December 8, 2024, 9:30 a.m. - 10:45 a.m.
Marriott Marquis San Diego Marina, Marriott Grand Ballroom 11-13

Alterations in the intestinal microbiome are linked to responses and outcomes following allogeneic hematopoietic cell transplantation (allo-HCT) and chimeric antigen receptor (CAR) T-cell therapy. This session will highlight emerging research investigating the host-microbiome axis in this context. We will assess factors that alter the intestinal microbiome in recipients of these cellular therapies, including diet and antibiotic exposure. Further, we will evaluate interventions to modulate the microbiome in this setting, namely fecal microbiota transplant.

Dr. Malard will discuss the role of fecal microbiota transplant in hematological malignancies, focusing on allo-HCT. He will provide an overview of the available clinical data on fecal microbiota transplant for treating graft-versus-host disease after allo-HCT. Dr. Malard will also discuss the potential of this procedure to prevent graft-versus-host disease and mitigate infection. He will also address the role of fecal microbiota transplant as a strategy to eradicate multidrug-resistant bacteria in patients who have undergone allo-HCT. Finally, the potential mechanism of action of fecal microbiota transplant and the implications of fecal microbiota transplant for CAR-T will be discussed.

Dr. David will share an approach for using metagenomic sequencing of fecal samples to track dietary intake in recipients of allo-HCT. He will illustrate how this method, FoodSeq, was initially tested using hospital-based foods. Dr. David will also show how FoodSeq was applied to a patient population, revealing reductions in food intake after allo-HCT. Notably, he will also demonstrate how these changes in food intake were linked to aspects of patient outcomes and microbiome changes following allo-HCT.

Dr. Andermann will explore how antibiotics influence the gut microbiome, the antimicrobial resistome (the collection of resistance genes in the gut), and immunologic/infectious outcomes in patients undergoing allo-HCT and CAR-T. She will review previous research findings and describe how anaerobically active antibiotics alter taxonomic and resistance gene composition in the gut during allo-HCT. Additionally, she will compare the spectrum of activity of antibiotics commonly used for febrile neutropenia, emphasizing the need for further research on how these antibiotics distribute throughout the gut lumen and drive changes in the abundance of commensal gut bacteria in recipients of cellular therapy.

Chair:

Melody Smith, MD,MS
Stanford University School of Medicine
Stanford, CA

Speakers:

Florent Malard, M.D., Ph.D.
Sorbonne Université, Hôpital Saint-Antoine, AP-HP, Service d'Hématologie Clinique et Thérapie Cellulaire,Centre de Recherche Saint-Antoine UMRs938
Paris, France
Fecal Microbiota Transplant As a Strategy to Mitigate Infection and Gvhd Following TCT

Lawrence A David, PhD
Duke University
Durham, NC
Deciphering Nutritional Intake from Metagenomic Data Using Computational Tools

Tessa Andermann, MD,MPH
University of North Carolina, Chapel Hill
Chapel Hill, NC
Impact of Antibiotic Exposure on Outcomes Following TCT

Newly Discovered Functions of Megakaryocytes and Platelets

Sunday, December 8, 2024, 4:30 p.m. - 5:45 p.m.
San Diego Convention Center, Room 29

This session will explore cutting-edge discoveries in platelet biogenesis and the pathological mechanisms underlying platelet-related disorders.

Key topics include the role of glycosylation in megakaryocyte (Mk) and platelet (PLT) functions and their involvement in disease. Focus will be placed on the role of sialic acid and galactose modifications in regulating megakaryocyte-primed hematopoietic stem cell function and megakaryocyte activity, especially in relation to thrombocytopenia, including immune thrombocytopenias. Additionally, novel insights into thrombo-inflammation will be discussed, highlighting how inflammatory processes contribute to thrombosis and platelet dysfunction. Emerging research on the role of megakaryocytes and platelets in bone marrow fibrosis will also be featured, shedding light on their dual function in both hematopoiesis and pathological fibrosis. These topics are highly relevant, particularly with ongoing advancements in understanding the basic mechanisms of platelet production, glycosylation, and the interaction between thrombosis and inflammation.

Dr. Karin Hoffmeister will discuss the role of sialic acid and galactose modifications in regulating megakaryocyte activity. These glycan decorations are crucial for maintaining proper megakaryocyte function and platelet production, with disruptions contributing to platelet clearance and immune-mediated destruction in conditions like immune thrombocytopenia (ITP).

Dr. Tobias Petzold will discuss novel insights on natural occurring resilience mechanism to prevent thromboinflammation as key pathomechanism in thrombotic diseases. By introducing the concept of long-term immobility induced thromboprotection we will learn from a novel animal model- the hibernating brown bear - that is protected from developing venous thrombosis during 6 months of immobility in winter.  These findings will be translated into the clinical context.

Dr. Anna Nam will discuss the impact of ER stress and the unfolded protein response on megakaryopoiesis and platelets due to mutations in CALR in essential thrombocythemia and myelofibrosis. Using advanced single-cell multi-omics approaches, we show that CALR mutations elicit the unfolded protein response in human. Targeting ER stress-related pathways leads to reduction in platelet burden in mouse models.

Chair:

Alessandra Balduini, MD
Tufts University
Medford, MA

Speakers:

Karin M. Hoffmeister, MD
Versiti Blood Research Institute, Milwaukee, WI
Milwaukee, WI
Unveiling the Sweet Side of Platelet Formation: Exploring the Pivotal Role of Glycans

Tobias Petzold, MD,MSc
Charité – Universitätsmedizin Berlin
Berlin, Germany
Regulation of Platelet Function During Immobilty

Anna S. Nam, MD
Weill Cornell Medicine
New York, NY
ER Stress in Megakaryopoiesis

Placing the Brakes on Accelerated Aging

Monday, December 9, 2024, 4:30 p.m. - 5:45 p.m.
San Diego Convention Center, Room 30

Hematologic disorders disproportionately affect older adults; despite this, our understanding of the implications of age on the pathogenesis and treatment of these diseases remains limited. The geroscience field is actively investigating geriomics to aid in distinguishing biological and chronological aging. This session will highlight biological aging assessments for hematologic disease which will be crucial for the identification of targets and development of therapies for this specific population.

Chair:

Ashley Rosko, MD
The Ohio State University
Columbus, OH

Speakers:

Els Mansell, PhD
Erasmus Medical Center
Rotterdam, Netherlands
Aging of Hematopoietic Stem Cells and Their Niche

Christin E Burd, PhD
Ohio State
Columbus, OH
Geroscience and Geri-Omics in Hematologic Malignancies

Marcel R.M. van den Brink, MD, PhD
City of Hope National Medical Center
Duarte, CA
Targeting Rejuvenation Therapies to Decelerate Aging

Special Symposium on the Basic Science of Hemostasis and Thrombosis

Monday, December 9, 2024, 4:30 p.m. - 6:00 p.m.
San Diego Convention Center, Room 31

This session will highlight emerging topics and the latest discoveries in regulating inflammation at the cross-section of hemostasis, platelets, and vascular biology.

Co-Chairs:

Laurent O. Mosnier, PhD
The Scripps Research Inst.
La Jolla, CA

Hartmut Weiler, PhD
Versiti Blood Research Institute
Milwaukee, WI

Lijun Xia, MD, PhD
Oklahoma Medical Research Foundation
Oklahoma City, OK

Speakers:

Yesim Dargaud, MD, PhD
Hopital Edouard Herriot Pav. E
Lyon, France
Efficacy of Platelet-Inspired Hemostatic Nanoparticles on Bleeding in Von Willebrand Disease Murine Model

Jieqing Zhu, PhD
Versiti Blood Research Institute
Milwaukee, WI
Platelet Integrin Structure, Function and Role in Disease

Yu Hou
Qilu Hospital, Cheeloo College of Medicine, Shandong University
Jinan, CHN
Platelet TGFb1 in the Pathogenesis of Immune Thrombocytopenia Purpura