What you need to know
A new grant from the National Institutes of Health and the National Cancer Institute will fund a physician-scientist from the Hackensack Meridian Center for Discovery and Innovation (CDI) to investigate ways to harness the body’s natural ability to create CAR (Chimeric antigen receptor) T cells for long-term treatment of pediatric blood cancers.
The $2.78 million grant will run over five years and will support the work of Johannes Zakrzewski, M.D., who is an associate member of the CDI and a pediatric stem cell transplant attending physician at Joseph M. Sanzari Children’s Hospital at Hackensack University Medical Center and the John Theurer Cancer Center, which is part of the NCI-designated Georgetown Lombardi Comprehensive Cancer Center.
The grant, entitled "Harnessing the Thymus for Long-term Tumor Control with Hematopoietic Stem Cell- derived Naive CAR T Cells," seeks to educate the thymus to manufacture tailored immune cells to continue to keep blood cancers in check for years after remission.
Zakrzewski and his team plan on implementing a novel platform for long-lasting tumor immunosurveillance based on continuous in-vivo generation of naïve CAR T cells.
About the Hypothesis
Their hypothesis: after the completion of the initial course of intensive chemotherapy, long-lasting T-cell immunity to cancer antigens can be established by using hematopoietic stem and progenitor cells (HSPCs) engineered to express a tumor cell-targeting CAR and delivered into the patient’s thymus.
The minimally invasive procedure would harness the thymus of cancer patients as an in-vivo bioreactor, offering an innovative and also relatively simple and low-toxic clinical method for sustainable production of highly potent naïve designer T cells from genetically-manipulated HSPCs.
The work is based on the laboratory’s years of published and unpublished data, all of which has been supported by various grants and groups, most recently the Tackle Kids Cancer program of the Hackensack Meridian Health Foundation.
Chimeric receptor antigen (CAR) T cells are transforming cancer treatment by providing tumor-specific, molecularly targeted therapies. But while the therapies can induce remission in most cases, long-term disease control remains a major clinical challenge - especially in pediatric and young adult cancer patients with high-risk malignancies.