Generation of Tailor-Made Leukemia Models in Immune-Competent Mice

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Address

The National Institute for Biotechnology
in the Negev Ltd.
Ben-Gurion University of the Negev

Introduction 

Leukemias are malignancies of the hematopoietic system that are affecting hundreds of thousands of kids and adults. While treatment options for some leukemia types are continuously improving, other types still have poor prognosis. Research with adequate models is needed for mechanistic understanding of leukemia initiation and progression, and for the development of new drugs. Genetically engineered mouse models offer few models that are not always obtainable. Patient Derived Xenotransplant (PDX) benefits having actual patient’s cells, but suffer from cross-species mismatches and lack the immune component which is largely involved in leukemia and essential for anti-cancer immunotherapies. Models that can give simple answers on the contribution of defined sets of Leukemia genetic drives in the setting of syngeneic immunocompetent mice are needed.

 

The Technology

The present technology relates to the generation of versatile, ready to use Leukemic cell-lines that can be easily evaluated in the setting of syngeneic immunocompetent C57BL/6 mice, or further developed for any laboratory animal. In order to generate multiple novel models for leukemia types, we use the lentiviral system for induced overexpression of severl oncogenic-factors in hematopoietic cells in vivo. Starting with defined Hematopoietic Stem Cells or defined progenitors that are FACS-sorted, we can introduce combinations of multiple oncogenic-factors and transplant the cells into a syngeneic mouse. As each cell picks few factors at random, multiple combinations are functionally tested by following the appearance of malignant leukemic outgrowth. Utilizing specific factors, we already generated a series of Leukemias, including Acute Myeloid Leukemia (AML), Chronic Lymphocytic Leukemia (CLL), and B-cell myeloma, which are yet most lethal and prevalent in human patients.

 

Advantages

  • A simple technology, ready for partnering.
  • The product can be “tailor-made”, using oncogenic-factor of interest.
  • The novel Leukemia-lines can be shipped as frozen vials and ready to be used (grow tumors) in vivo in syngeneic immune-competent C57BL/6 mice.
  • Unlike PDX Can be used to evaluate immune oncology compounds.

 

Principal Investigator

Dr. Roi Gazit, NIBN and the Shraga Segal Department of Microbiology Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Israel