St. Jude Reference #SJ-21-0020
The emerging field of Natural Killer (NK) cell-based therapeutics has been hampered by inefficient transduction methods, resulting in the generation of variable and unreliable NK cells. Researchers at St. Jude have developed an invention to enhance NK cell modification techniques.
The invention uses MRT67307 to allow for the transduction of NK cells by VSV-G pseudotyped lentiviral vectors. MRT67303 is a chemical compound that is a specific inhibitor of TBK1 and IKK epsilon which are downstream of the endosomal TLR4 pathway. TLR4 binds the glycoprotein G protein of the VSV-G envelope. This compound blocks an innate immune response that leads to NK cell over stimulation and death.
This novel, single agent, method allows for and enhances NK cell transduction using VSV-G lentiviruses. Further it is an improvement over the state of the art, as MRT67307 is significantly more specific and can be used at lower concentrations than other previously reported compounds. It is a simple reversibly binding agent that is transiently used to allow for a permanent modification of NK cells with lentivirus. This approach could readily be translated into clinical grade production of genetically modified NK cells, with the potential to significantly impact the NK cell therapy field.
Immunotherapy, enhance ease and efficiency of NK cell modifications, VSV-G pseudotyped lentiviral vector, MRT67303, inhibit TBK1 and IKK epsilon, glycoprotein G protein, improvement over BX-795.
Granted patents or published applications
Application filed, available under confidentiality
Related scientific references
Peter Chockley, Sagar L Patil, Stephen Gottschalk; “Transient blockade of TBK1/IKKε allows efficient transduction of primary human natural killer cells with vesicular stomatitis virus G-pseudotyped lentiviral vectors;” Cytotherapy, 2021 Sep;23(9):787-792. doi: 10.1016/j.jcyt.2021.04.010. Epub 2021 Jun 9.
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