Technology ID

Genetic Manipulation of Natural Killer Cells to Express c-MPL Growth Factor Receptor as a Therapy for Cancer

Lead Inventor
Allan, David (YM BioSciences Inc)
Childs, Richard (NHLBI)
Research Materials
Therapeutic Areas
Development Stages
Pre-Clinical (in vitro)
Research Products
Research Equipment
Lead IC

This technology includes genetic manipulation of natural killer (NK) cells to express thrombopoietin receptor (c-MPL) growth factor receptor as strategy to augment NK cell proliferation and anti-tumor immunity. Many investigational adoptive immunotherapy regimens utilizing NK cells require the administration of IL-2 or IL-15 cytokines to support the survival and function of the cells in patients, however administration of these cytokines causes a number of serious dose-dependent toxicities. In the presence of thrombopoietin (TPO) ligand, lentiviral transduction of primary human NK cells to express c-MPL enhanced in vitro cellular proliferation and increased degranulation and cytokine production towards target cells. Data from our study could be translated to a clinical trial setting, where the infusion of genetically modified c-MPL-expressing NK cells is followed by the off-label administration of an FDA-approved TPO-mimetic (e.g., eltrombopag, romiplostim).

Commercial Applications
  • NK immunotherapy using cells trans-genetically modified to express c-MPL for a large number of hematological malignancies
  • CAR-T immunotherapy cells modified to express c-MPL
  • TCR-transgenic T cells modified to express c-MPL
  • CD34+ hematogenic stem and progenitor cells modified to express mutated c-MPL (iii of section 7) to facilitate selective eltrombopag-mediated expansion after transplant relative to unmodified endogenous stem cells
Competitive Advantages
Treatment of patients with c-MPL-modified NK cells may reduce or eliminate the necessity for IL-2 administration, which can cause severe toxicity, and allow for the specific pharmacological stimulation of infused modified cells but not endogenous immune cells, while simultaneously boosting their anti-tumor function.
Licensing Contact:
Shmilovich, Michael