[Federal Register Volume 82, Number 93 (Tuesday, May 16, 2017)]
[Notices]
[Page 22554]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-09792]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Invention; Availability for Licensing

AGENCY: National Institutes of Health, HHS.

ACTION: Notice.

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SUMMARY: The inventions listed below are owned by an agency of the U.S. 
Government.

FOR FURTHER INFORMATION CONTACT: Licensing information may be obtained 
by emailing the indicated licensing contact at the National Heart, 
Lung, and Blood, Office of Technology Transfer and Development Office 
of Technology Transfer, 31 Center Drive Room 4A29, MSC 2479, Bethesda, 
MD 20892-2479; telephone: 301-402-5579. A signed Confidential 
Disclosure Agreement may be required to receive any unpublished 
information.

SUPPLEMENTARY INFORMATION: The following inventions are available for 
licensing in accordance with 35 U.S.C. 209 and 37 CFR part 404 to 
achieve expeditious commercialization of results of federally-funded 
research and development. Technology description follows.

T-Cells Transduced With HLA A11 Restricted CT-RCC HERV-E Reactive TCR 
To Treat Patients With ccRCC

    Description of Technology: We isolated an allogeneic T cell clone 
from a clear cell renal cell carcinoma (ccRCC) HLA-A11 patient who 
showed prolonged tumor regression after an allogeneic transplant. This 
clone was found to have tumor specific cytotoxicity, killing patient's 
tumor cells in vitro. We found that antigen recognized by this clone is 
an HLA-A11 restricted peptide (named CT-RCC-1) and it is encoded by a 
novel human endogenous retrovirus-E (named CT-RCC HERV-E) whose 
expression was discovered to be restricted to ccRCC, but not observed 
in normal tissues or other tumor types. We observed that more than 80% 
of ccRCC tumors express CT-RCC HERV-E provirus, which makes it an ideal 
target for T cell based immunotherapy. We have sequenced and cloned the 
genes for a T cell receptor (TCR) that specifically recognizes an HLA-
A11 restricted CT-RCC-1 antigen. We then created a retroviral vector 
encoding this TCR as well as a truncated CD34 protein lacking the 
intracellular domain, which can be used to facilitate the isolation of 
T-cells transduced with this TCR. Phase I/II clinical trials are 
currently being planned in patients with metastatic ccRCC using normal 
patient's T-cells transduced with this vector.
    Potential Commercial Applications: The vector can be used to 
transduce and expand normal T cells from HLA-A11 patients with 
metastatic ccRCC with the TCR recognizing HLA-A11-restricted CT-RCC 
HERV-E antigen that specifically expressed on clear cell type of kidney 
cancer. The transduced cytotoxic T cells can then be administered to 
subjects to treat or inhibit metastatic kidney cancer. Kidney cancer is 
responsible for approximately 12,000 deaths every year in the United 
States alone. As with most cancer, when detected at early stages, 
surgical intervention is highly effective. Despite progress in treating 
kidney cancer with IL-2 and inhibitors of immune checkpoints, 
metastatic ccRCC is generally lethal, with mean survival being less 
than a year. Patients with melanoma and other malignancies can now 
benefit from adoptive T cell transfer. One of the limitations of this 
approach for metastatic kidney cancer is a lack of identified tumor 
restricted antigens for this tumor. We show that the CT-RCC HERV-E is 
expressed in most ccRCC tumors but not in normal tissues which makes 
the antigens encoded by this provirus ideal targets for T cell-based 
immunotherapy of ccRCC.
    Development Stage: Early-stage; In vitro data available.
    Inventors: Richard W. Childs and Elena Cherkasova (NHLBI), Michael 
Nishimura (Loyola University Chicago).
    Publications:
    1. Takahashi Y. et al. 2008. Regression of kidney cancer following 
allogeneic stem-cell transplantation associated with T-cells 
recognizing a HERV-E antigen. J. Clin. Invest. 118:1099-109.
    2. Cherkasova E. et al. 2011. Inactivation of the von Hippel-Lindau 
tumor suppressor leads to selective expression of a human endogenous 
retrovirus in kidney cancer. Oncogene 30:4697-706.
    3. Cherkasova E. et al. 2013. Endogenous retroviruses as targets 
for antitumor immunity in renal cell cancer and other tumors. Front. 
Oncol. 3:243-247.
    4. Cherkasova E. et al. 2016. Detection of a HERV-E envelope with 
selective expression in clear cell kidney cancer. Cancer Res. 76:2177-
2185.
    Intellectual Property: NIH Reference No. E-120-2016/0--US 
Application No. 62/357,265, filed June 30, 2016.
    Licensing Contact: Cristina Thalhammer-Reyero, Ph.D., M.B.A.; 301-
435-4507; [email protected].

    Dated: May 2, 2017.
Cristina Thalhammer-Reyero,
Senior Licensing and Patenting Manager, Office of Technology Transfer 
and Development, National Heart, Lung, and Blood Institute.
[FR Doc. 2017-09792 Filed 5-15-17; 8:45 am]
 BILLING CODE 4140-01-P