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Adoptive T-Cell Transfer After Lymphodepletion Promotes Tumor Regression

Posted Jun 15 2010 5:00pm

Description of Invention:
Available for licensing is a method of adoptive cell transfer (ACT) immunotherapy. Since its first description, ACT is now being developed for the supportive treatment of a variety of infectious diseases and cancer.

Current ACT methods to treat cancer are based on the ex vivo selection of lymphocytes with high avidity for recognition of tumor antigens, and their activation and numerical expansion before re-infusion to the autologous tumor-bearing host. The current invention improves ACT by including a pre-treatment regimen to ensure permissive conditions in the host for in vivo proliferation of the transferred cells. Specifically, the immune system is suppressed by pre-treatment with lymphodepleting chemotherapy. Two separate clinical trials have demonstrated that using this approach, ACT can induce lasting tumor shrinkage.

Lymphodepleting chemotherapy followed by ACT resulted in tumor shrinkage of at least 50 percent in 6 out of 13 treated patients suffering from refractory melanoma. Several patients remained cancer free for more than a year after treatment. The usefulness of combined ACT and lymphodepleting therapy for cancer treatment was confirmed when this study was extended to include 35 melanoma patients. Eighteen of the 35 patients (51%) responded to the treatment, including 3 patients who experienced ongoing complete disappearance of cancer and 15 patients had tumor shrinkage of at least 50 percent with a mean duration of almost a year after treatment. In a recent clinical trial that is not yet published, using a modified protocol to treat 23 patients, a similar response rate (56%) was seen.

This approach to ACT offers a potentially significant improvement in the treatment of many types of cancer. In addition, this method might be applicable in treating other diseases such as AIDS, immunodeficiency, or other autoimmunity for which immune effector cells can impact the clinical outcome.

Inventors:
Mark E Dudley (NCI)
Steven A Rosenberg (NCI)
John R Wunderlich (NCI)


Patent Status:
HHS, Reference No. E-275-2002/1
US, Application No. 10/526,697 filed 05 May 2005 , claiming priority to 06 Sep 2002


Relevant Publication:
  1. 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 ]
  2. ME Dudley et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002 Oct 25;298(5594):850-854. [ PubMed abs ]


Licensing Status:
Available for 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 ACT therapy. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.


Portfolios:
Cancer
Cancer - Therapeutics
In-vivo Data



For Additional Information Please Contact:
Samuel Bish Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: bishse@mail.nih.gov
Phone: 301-435-5282
Fax: 301-402-0220


Ref No: 673

Updated: 06/2010

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