Marquee Sessions and Lectures

ASH-EHA Joint Symposium: Novel Approaches to Cell Engineering in Hematopoietic Cell Transplantation

A deeper understanding of the biology of immune mechanisms has resulted in a number of approaches to engineer the hematopoietic graft to improve outcomes for patients undergoing allogeneic hematopoietic cell transplantation. In this session we will review different strategies employed throughout the world examining biological mechanisms, strategies, and clinical outcomes. These approaches offer the possibility of reduced complications such as non-relapse mortality and graft vs host disease with less toxicity. Additional approaches to reduce relapse and improve immune reconstitution are under development and will be discussed.

Best of ASH

E. Donnall Thomas Lecture and Prize

Ernest Beutler Lecture and Prize

Ham-Wasserman Lecture

CAR T cell therapy has become a transformational treatment for patients with B cell malignancies and multiple myeloma. However, CAR T cell-based therapies for T cell malignancies has been more challenging. CD7-targeted chimeric antigen receptor (CAR) T-cell therapy represents a novel immunotherapeutic approach for relapsed or refractory T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) which are aggressive malignancies with poor outcomes despite conventional salvage treatments. CD7, a transmembrane glycoprotein expressed in over 95% of T-ALL/LBL cases, constitutes an ideal therapeutic target; however, its expression on normal T cells necessitates innovative engineering strategies to overcome CAR-T cell fratricide. Dr. Lu will discuss the very encouraging results including autologous naturally selected constructs, donor-derived products, and universal “off-the-shelf” products that could make a CAR T cell therapy for T cell disease a therapeutic reality. Across all platforms, CD7 CAR-T therapy demonstrated potent initial antileukemic activity, achieving complete remission (CR) rates of 80–95%. Nevertheless, durable disease control remains critically dependent on consolidative allogeneic hematopoietic stem cell transplantation. Notably, CD7-negative relapse accounted for 30–60% of treatment failures, emphasizing antigen escape as a primary resistance mechanism. Dr. Lu will discuss hallenges and future directions with the hope that global availability of CD7 CAR-T therapies will be available in the near future for this high-risk patient population.

Chair:

Robert Negrin, MD

Speaker:

Peihua Lu
Beijing Lu Daopei Hospital
Beijing, China
CD7 CAR-T Therapy in T-cell Acute Leukemia/Lymphoma: Past, Present and Future

Presidential Symposium

Peripheral immune tolerance is an active state of unresponsiveness to antigens that should elicit an adaptive immune response. Suppression of fetus-specific cytotoxic T cells during pregnancy and suppression of self-reactive T cells that escape central tolerance and might otherwise cause autoimmune disease are classic examples of such tolerance.  Cancers can induce tumor-specific immune tolerance and thereby evade immune attack. The critical importance of immune tolerance was recently acknowledged in the awarding of the Nobel Prize for the discovery of FoxP3+ regulatory T cells (Tregs) and their requisite role in peripheral tolerance. Surprisingly, the mechanism responsible for inducing such tolerance has remained elusive.  Recently, Dr. Engleman identified an unexpected role erythropoietin (EPO) acting through EPO receptors (EPOR) on conventional Type 1 dendritic cells (cDC1s) and macrophages to promote their tolerogenic maturation and activation of antigen-specific Tregs. EPOR signaling in these dendritic cells induces tolerance to allogeneic organ transplants and fetuses and ameliorates graft versus host disease in mice. On the other hand, blockade of EPOR on these cells results in the loss of tolerance and induction of a cytotoxic T cell response that can cause regression of tumors. These findings suggest that antagonists and agonists targeting EPOR on cDC1s and macrophages may prove useful in the treatment of disorders ranging from cancer and infection to autoimmune disease and allograft rejection.

The thymus which was thought to involute and become non-functional over the course of one’s lifetime has become the focus of new inquiry challenging this conventional teaching. Recent findings indicate that thymic function has significant impact on health and disease throughout life representing a novel paradigm of immune function. In this session Dr. Scadden will discuss how the thymus may affect the outcome of hematologic malignancies, alter sensitivity to immunologic therapies and review current efforts to improve thymus function. 

Dr Fyodor Urnov will describe the use of platform approaches to engineer CRISPR-gene editing based ex vivo and in vivo therapies on-demand for severe pediatric inborn errors of immunity. The development of gene therapy approaches to treat some of the most challenging genetic disorders represents a culmination of decades of research on the biology, pathophysiology and creative application of basic scientific concepts to the treatment of complex diseases. The hope that these may be addressed using therapies developed in the body of the patient represent a truly transformational approach that could have broad applicability.

Chair:

Robert Negrin, MD

Speakers:

Edgar Engleman
Stanford University School of Medicine
Palo Alto, United States
Role of EPO/EPOR in Tolerance Induction

David T Scadden, MD
Harvard Stem Cell Institute
Cambridge, United States
Role of the Adult Thymus in Health and Disease

David T Scadden, MD
Massachusetts General Hospital
Boston, United States
Role of the Adult Thymus in Health and Disease

Fyodor Urnov
University of California, Berkeley
Berkeley, United States
Novel Approaches to in vivo Therapy