Enriched Natural Killer Cells for Adoptive Infusion Cancer Therapy


Immuno-therapy has taken a lead among the new cancer therapeutic approaches. It is one of the most promising new therapeutic approaches that exploit the innate immune mechanism of an individual to fight against a certain disease.

Natural killer (NK) cells are a form of cytotoxic lymphocytes which constitute a major portion of the innate immune system. NK cells have tumor cytotoxic properties independent of tumor specific antigens and have been shown in murine models to control and prevent tumor growth and dissemination. Inactivation of NK cells potentially allows cancer cells to evade host NK-cell-mediated immunity. Ligation of killer immunoglobulin like receptors (KIRs) by MHC class I on both normal and malignant tissues suppresses the function of NK cells.

The present invention relates to treating cancer and other hyperproliferative disorders by administering an enriched composition of allogeneic or autologous (KIR/KIR ligand incompatible) NK cell population. This enriched composition can potentially override the inactivation of NK cells by self HLA molecules or MHC class I expressing tumors. Claims cover compositions of enriched NK cell populations and method of treating malignancies or prevent recurrence of malignancies and treating any hyperproliferative disorders with these enriched compositions. Claims also cover a method to sensitize malignancies to NK cell TRAIL-mediated killing by pretreatment with bortezomib.

Potential Commercial Applications: Competitive Advantages:
  • New adoptive infusion immunotherapeutic method for treating solid tumors
  • New cancer treatment method exploiting the function of NK cells
  • Enriched composition of allogeneic and autologous NK cell population
  • Enriched NK cell composition has potential to override the natural NK cell inactivation process by HLA or MHC class I expressing tumors
  • Sensitizing cancers to adoptively infused NK cells by treatment with bortezomib as a method to sensitize to NK cell TRAIL cytotoxicity
 


Development Stage:
The technology is currently in the pre-clinical stage of development.

Inventors:

Richard Childs (NHLBI)  ➽ more inventions...


Intellectual Property:
PCT Application No. PCT/US2005/039282
US Application No. 14/058,000

Publications:
T Igarashi et al. Enhanced cytotoxicity of allogeneic NK cells with killer immunoglobulin-like receptor ligand incompatibility against melanoma and renal cell carcinoma cells. Blood. 2004 Jul 1;104(1):170-177. PubMed: 15016654
A Lundqvist et al. Bortezomib and depsipeptide sensitize tumors to tumor necrosis factor-related apoptosis-inducing ligand: a novel method to potentiate natural killer cell tumor cytotoxicity. Cancer Res. 2006 Jul 15;66(14):7317-7325. PubMed: 16849582
A Lundqvist et al. Reduction of GVHD and enhanced anti-tumor effects after adoptive infusion of alloreactive Ly49-mismatched NK-cells from MHC-matched donors. Blood. Prepublished online 2006 Dec 19, doi 10.1182/blood-2006-05-024315. PubMed: 17179231

Collaboration Opportunity:

The Hematology Branch of the National Heart, Lung, and Blood Institute is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of in vitro expanded adoptively infused NK cells to treat advanced and incurable cancers. Please contact Dr. Richard W. Childs at 301/496-5093 or 301/451-7128 (email: childsr@nih.gov) for more information.


Licensing Contact:
Denise Crooks,
Email: crooksd@mail.nih.gov
Phone: 301-435-0103

OTT Reference No: E-183-2004-1
Updated: Sep 30, 2010