2021 TCT | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR
 

Lectures
 

Mortimer M. Bortin Lecture
Friday, February 12, 2021 (11:00 AM – 11:30 AM CT)
 
 
 
T Cell Immunotherapy via Native and Chimeric Receptors
 
 
Presented by Helen E. Heslop, MD

Cellular immunotherapies have immense potential as they can specifically target tumor antigens through native or artificial receptors. We have evaluated expanded T cells recognizing tumor antigens though their native receptor to target viruses such as EBV,ADV or CMV that cause morbidity and mortality after transplant with encouraging response rates when using donor derived cells post-transplant. More recent studies have infused closely matched third-party virus-specific T cells and reported encouraging response rates between 50 and 90%. As most tumors do not express viral antigens we have also evaluated tumor-associated antigens (TAAs) which are expressed by many malignancies but otherwise are found only in germline tissues that are immune privileged and therefore not susceptible to T-cell attack. We have used peptide libraries that can present both HLA-class I- and class II-restricted epitopes to reactivate TAA-specific T cells and to overcome the possibility of tumor escape by targeting multiple epitopes in 5 antigens in clinical trials in lymphoma, myeloma and acute leukemia. Chimeric antigen receptors may also be used to genetically modify T cells and strategies targeting CD19 are highly successful against B-cell non-Hodgkin lymphomas and acute lymphoblastic leukemia. The development of equivalent adoptive cell therapies (ACTs) that target malignancies of T-cell origin is a challenge due to shared expression of most targetable surface antigens between normal and malignant T cells, potentially leading to fratricide of CAR T cells or profound immunodeficiency. We are currently evaluating CD30 as a target expressed on only a subset of T cells and CD5.  

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E. Donnall Thomas Lecture
Friday, February 12, 2021 (11:30 AM – 12:00 PM CT)
 
 
 
Cord Blood: Forerunners and New Horizons
 
 
Presented by Elizabeth J. Shpall, MD

Umbilical cord blood (CB) has emerged as a valuable source of hematopoietic support for patients with high-risk hematologic diseases lacking an human leukocyte antigen (HLA)-matched bone marrow donor. The first successful CB transplant was performed in 1989 by Dr. Eliane Gluckman and colleagues. Since then many CB transplants have been performed world-wide in both pediatric and adult patients. The ethnic diversity, relative ease of collection, ready availability as cryopreserved units as well as tolerance of higher degrees of HLA disparity between donor and recipient, are positive attributes of CB when compared to bone marrow or mobilized peripheral blood progenitor cells (PBPCs). There were major limitations of CB transplantation identified in the early studies, however, which included a low cell dose with associated delays in engraftment, and delays in immune reconstitution resulting in high rates of infectious complications. Graft versus host disease (GVHD) also remained a concern, particularly in adult patients. In response to these complications there have been many novel therapeutic strategies that have been developed including the ex vivo expansion of CB hematopoietic stem and progenitor cells, as well as CB-derived immune cells to improve clinical outcomes. Currently the number of CB units in the global CB Bank inventories exceeds 1.5 million and thus there are large numbers available for cellular therapies beyond stem cell transplantation. These CB units are now being used to generate potent immunotherapies including CB-derived natural killer cells and T cells which appear promising in early studies against many different cancers. Additionally CB derived mesenchymal stem cells (MSC) and MSC-derived exosomes are showing promise for GVHD, regenerative medicine and as effective vehicles for therapeutic gene delivery.  

View Dr. Shpall's full bio