Adoptive Immunotherapy with Autologous Natural Killer Cells
Description of Invention:
Dr. Rosenberg and colleagues have clearly demonstrated that T-lymphocytes can mediate the regression of metastatic melanoma. However, not all patients with cancer are eligible for or respond to this type of immunotherapy. In some patients, the tumor infiltrating lymphocytes (TIL) do not expand sufficiently, or do not exhibit sufficient tumor specific reactivity.
Studies in mice have shown that adoptive transfer of NK cells activated in vitro can significantly reduce the load of Acute Myelogenous Leukemia (AML), and intravenously-injected autologous NK cells have been shown to significantly decrease melanoma tumor outgrowths. To this end, Dr. Rosenberg and colleagues have developed an alternative type of immunotherapy, which involves the adoptive transfer of autologous natural killer (NK) cells. This method consists of three parts: a) Isolation and expansion of NK cells ex-vivo; b) Administration of nonmyeloablative lymphodepleting chemotherapy regimen to the patient; and c) Reconstitution of the patient’s immune system by infusion of NK cells and interleukin 2. This approach also offers the possibility of treating AIDS, immunodeficiency, and autoimmune diseases for which immune cells can impact the clinical outcome.
Development Status:
This work has not yet been published; however, Dr. Rosenberg and colleagues have developed a clinical protocol and are awaiting IRB approval to begin enrolling patients in a Phase I clinical trial.
Inventors:
Steven A. Rosenberg and Maria R. Parkhurst (NCI)
Patent Status:
DHHS Reference No. E-090-2006/0 --
U.S. Provisional Application No. 60/779,863 filed 06 Mar 2006
PCT Application No. PCT/US2007/063352 filed 06 Mar 2007, which published as WO 2007/103901 on 13 Sep 2007
SA Rosenberg and ME Dudley. Cancer regression in patients with metastatic melanoma after the transfer of autologous antitumor lymphocytes. Proc Natl Acad Sci USA. 2004 Oct 5;101 Suppl 2:14639-14645. [PubMed abs.]
ME Dudley et al. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol. 2005 Apr 1;23(10):2346-2357. [PubMed abs.]
U Siegler et al. Activated natural killer cells from patients with acute myeloid leukemia are cytotoxic against autologous leukemic blasts in NOD/SCID mice. Leukemia 2005 Dec;19(12):2215-2222. [PubMed abs.]
F Lozupone et al. Effect of human natural killer and gammadelta T cells on the growth of human autologous melanoma xenografts in SCID mice. Cancer Res. 2004 Jan 1;64:378-385. [PubMed abs.]
Licensing Status: Available for non-exclusive or exclusive licensing.
Collaborative Research Opportunity:
The NCI Surgery Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Natural Killer (NK) cells for their clinical use as cancer treatments. Please contact Dr. Steven Rosenberg at (301) 496-4164 or sar@mail.nih.gov for more information.
Portfolios: Gene Based Therapies Cancer
Gene Based Therapies -Therapeutics-Gene Therapy-Vectors-Viral vectors Cancer -Therapeutics-Gene Therapy-Genes Gene Based Therapies -Therapeutics-Gene Therapy-Vectors Gene Based Therapies -Therapeutics-Gene Therapy-Therapeutic Genes Cancer -Therapeutics-Gene Therapy Gene Based Therapies -Therapeutics-Gene Therapy Cancer -Therapeutics Gene Based Therapies -Therapeutics
For Additional Information Please Contact: Mojdeh Bahar J.D.
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