Natural killer (NK) cells are part of the innate immune system with the unique ability to distinguish normal cells from abnormal cells without prior priming. They are the first line of defense against viruses and play an important role in tumor surveillance. 

Over the past 50 years, remarkable progress has been made in our understanding of natural killer cell biology. These advances include a better understanding of the molecular and cellular basis for the recognition of “normal” vs. abnormal cells by NK cells, including the interaction of NK receptors with their cognate ligands, as well as the mechanisms by which NK cells crosstalk with other immune cells to orchestrate a strong immune response. The detailed knowledge that has emerged from these studies has served as the foundation for the subsequent efforts to exploit NK cells in hematopoietic stem cell transplantation for hematologic malignancies and, more recently, for adoptive cell therapy.

Adoptive cell therapy, involving the infusion of ex vivo expanded or selected autologous or allogeneic lymphocytes, tumor-infiltrating lymphocytes, or genetically modified lymphocytes, has shown great promise for the treatment of certain types of cancer. We live in exciting times where access to single-cell proteo-genomics data and technological advances in genetic engineering, synthetic biology, and cell manufacturing have resulted in a paradigm shift in our approach to cancer therapy. 

Natural killer cells offer unique characteristics that make them advantageous for adoptive cell therapy. These include an innate anti-tumor cytotoxicity as well as an excellent safety profile with minimal risk of graft-versus-host disease in the allogenic setting, thereby offering the promise of off-the-shelf cell therapy at large scale.

This lecture will focus on the progress that has been made in the application of NK cell immunotherapy and novel cell engineering strategies for the treatment of cancer. 

ASH will recognize Katy Rezvani, MD, PhD, of the University of Texas MD Anderson Cancer Center, with the 2023 E. Donnall Thomas Lecture and Prize. Dr. Rezvani is being honored for her paradigm-shifting approach of modifying natural killer cells derived from umbilical cord blood, which has the potential to reduce toxicity, lower the cost of therapy, and increase patient access to potentially life-saving cancer immunotherapies.