Dynein inhibition for enhanced anti-tumor cytotoxicity in solid tumors

This technology is a method for treating solid tumors that relies on dynein inhibition to enhance natural killer (NK) cell cytotoxicity.

Unmet Need: Enhanced lethality in immunosuppressive tumor microenvironments

The development of immunotherapies for cancer treatment has led to improvements in patient outcomes in several types of cancer. Unfortunately, the tumor microenvironment of solid tumors can be highly immunosuppressive, limiting the efficacy of immunotherapy in these tumors. Current research focuses on targeting specific mechanisms of immunosuppression in the tumor microenvironment to improve immunotherapy response rates; however, this approach yields varying results in different tumors due to the diverse immunosuppressive mechanisms present in distinct tumor microenvironments. Thus, there is a need for therapies that can enhance immune cell cytotoxicity despite immunosuppression induced by the tumor microenvironment.

The Technology: Inhibiting dynein for enhanced natural killer cell cytotoxicity in solid tumors

This technology is a therapeutic approach that blocks dynein function to amplify the ability of natural killer (NK) cells to kill cells in solid tumors. Blocking dynein function induces the dispersion of lytic granules, resulting in rapid and enhanced NK cell cytotoxicity. Since this technology modifies and amplifies the ability of NK cells to kill tumor cells, it can be effective independent of the specific immunosuppressive pathways induced by the tumor microenvironment. As such, this technology can be used to directly boost anti-tumor cytotoxicity or in combination with other cellular therapies to improve their efficacy in treating solid tumor malignancies.

Applications:

• Treatment for solid tumors
• Adjuvant treatment for existing therapies for solid tumors
• Research tool for studying the regulation of natural killer (NK) cell cytotoxicity
• Research tool for studying dysregulation of NK cells in autoimmune diseases
• Potential treatment for viral infections

Advantages:

• Does not target specific immunosuppressive pathways
• Enhances the lethality of NK cells
• Can be used in different tumor microenvironments
• Can be used alone or in combination with other cancer treatments

Lead Inventor:

Jordan Scott Orange, M.D.

Patent Information:

Patent Pending

Related Publications:

• Hsu H, Mace EM, Carisey AF, Viswanath DI, Christakou AE, Wiklund M, Onfelt B, Orange JS. “NK cells converge lytic granules to promote cytotoxicity and prevent bystander killing.” J Cell Biol. 2016 Dec 19; 215(6): 875–889.

• Mentlik AN, Sanborn KB, Holzbaur EL, Orange JS. “Rapid Lytic Granule Convergence to the MTOC in Natural Killer Cells Is Dependent on Dynein But Not Cytolytic Commitment.” Mol Biol Cell. 2010 Jul 1; 21(13): 2241–2256.

Tech Ventures Reference:

• IR CU24341

• Licensing Contact: Jerry Kokoshka