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Enhanced Development of Functional Human Natural Killer Cells for Pre-Clinical Study in the Greiner and Brehm Labs

Date Posted: Thursday, September 08, 2022

The laboratories of Dale Greiner, PhD and Michael Brehm, PhD in the UMass Chan Diabetes Center of Excellence, specialize in the creation and utilization of ‘humanized” mouse models used for pre-clinical study. Their research is focused on understanding human immune responses, both how to turn them off for the treatment of type 1 diabetes and autoimmunity, and conversely, using the same pathways to turn on immune responses for cancer treatments.

Immunotherapy has revolutionized the treatment of human disease and has improved survival rates for several cancers. There are still many cancer patients for whom current immunotherapies are not yet available.  A newly published study in the journal Federation of American Societies for Experimental Biology (FASEB) describes a new humanized mouse model that enhances the development of Natural Killer (NK) cells), which are emerging as key targets for cancer immunotherapy

                                 Michael Brehm, PhD           Dale Greiner, PhD

“We can generate human immune systems inside of our mice to understand why these systems develop the way they do and how they function,” said Dr. Greiner, the Dr. Eileen L. Berman and Stanley I. Berman Foundation Chair in Biomedical Research, Professor of Molecular Medicine and co-director of the UMass Chan Diabetes Center of Excellence. “We can take a tumor from any individual patient for whom chemotherapy and standard therapeutic approaches have failed, grow that tumor into dozens of mice, and test whatever drugs we want.”

“The human innate immune system plays a critical role in immunoregulation within the tumor microenvironment,” said Dr. Brehm, Associate Professor of Molecular Medicine and co-director of the Humanized Mouse Core Facility at UMass Chan. ”A limitation of using humanized mice in cancer research had been the lack of development and survival of NK cells after engrafting hematopoietic stem cells or peripheral blood mononuclear cells into the mice.”

In this study, the Brehm & and Greiner labs describe a novel humanized mouse model with improved NK cell acceptance and functionality. Their data explains the potential for this in vivo model to study human NK cell biology and to test new human-specific immune-therapies that target NK cells.

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