Immunotherapy and Nanotechnology-Enhanced Molecular Therapy of Acute Myeloid Leukemia and Multiple Myeloma

ABSTRACT

One of the major limitations to using immunotherapeutic modalities for the therapy of acute myeloid leukemia (AML) has been the lack of suitable targets on the surface of AML cells. Our laboratory recently identified B cell maturation protein (BCMA) on the surface of AML cells, a protein that has not been previously recognized as potential AML immunotherapy target. The protein is one the most sought-after targets for immunotherapy of MM, and there are currently more than 50 active clinical trials pursuing the development of immunotherapies targeting this protein in the context of treatment refractory MM. We validated BCMA expression by AML cells on the RNA and protein level and demonstrated preclinical in vitro and in vivo efficacy of BCMA directed T cell engager therapy of AML. While we are working toward repurposing of established BCMA directed therapeutics, which has the advantage that the timeline to clinical trials can be significantly accelerated, we are also developing a nanoparticle-BCMA antibody conjugate as a drug delivery platform for MM and AML specific targeted delivery of small molecule inhibitor compounds with potent anti-leukemia/myeloma properties.

BIOGRAPHY

Dr. Zakrzewski obtained an MD degree from the Friedrich-Alexander University (Germany) in 2000, followed by five years of training in Pediatrics and Pediatric Hematology/Oncology in Germany. He joined Memorial Sloan Kettering Cancer Center (MSKCC) in 2004 as a Research Fellow, studying the immunology of allogeneic hematopoietic stem cell transplantation. From 2008 to 2012 Dr. Zakrzewski repeated his clinical training at SUNY Downstate Medical Center and at MSKCC, before being appointed as an Assistant Member/ Assistant Attending Physician (Pediatric Bone Marrow Transplantation) at MSKCC from 2012 to 2017. He joined HMH’s Center for Discovery and Innovation (CDI) as an Associate Member in 2018 and has served as an Attending Physician in Pediatric Stem Cell Transplantation at Hackensack University Medical Center since 2019. Dr. Zakrzewski has additional appointments as an Associate Professor of Pediatrics at Hackensack Meridian School of Medicine and as an Associate Professor of Oncology at Georgetown University School of Medicine. His laboratory is NCI funded and studies the development of novel immunotherapies for blood cancers.

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