Government-Owned Inventions; Availability for Licensing, 50926-50928 [E6-14184]
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50926
Federal Register / Vol. 71, No. 166 / Monday, August 28, 2006 / Notices
Estimated
number of responses per
respondent
Estimated
number of
respondents
Type of respondents
Average burden hours per
response
Estimated total
annual burden
hours
requested
Blood donors at Baseline Visit ........................................................................
Blood donors at Follow-up Visit .......................................................................
3,750
1720
1
1
0.12
0.1
450
172
Total ..........................................................................................................
........................
........................
........................
622
Request for Comments: Written
comments and/or suggestions from the
public and affected agencies should
address one or more of the following
points: (1) Whether the proposed
collection of information is necessary
for the proper performance of the
function of the agency, including
whether the information will have
practical utility; (2) The accuracy of the
agency’s estimate of the burden of the
proposed collection of information,
including the validity of the
methodology and the assumptions used;
(3) Ways to enhance the quality, utility,
and clarity of the information collected;
and (4) Ways to minimize the burden of
the collection of information on those
who are to respond, including the use
of appropriate automated, electronic,
mechanical, or other technological
collection techniques or other forms of
information technology.
FOR FURTHER INFORMATION CONTACT: To
request more information on the
proposed project or to obtain a copy of
the data collection plans and
instruments, contact Dr. George Nemo,
Project Officer, NHLBI, Two Rockledge
Center, Room 10142, 6701 Rockledge
Drive, MSC 7950, Bethesda, MD 20892–
7950, or call 301–435–0075, or e-mail
your request to nemog@nih.gov.
Comments Due Date: Comments
regarding this information collection are
best assured of having their full effect if
received within 60 days of the date of
this publication.
Dated: August 21, 2006.
Meg Scofield,
NHLBI Project Clearance Liaison Officer,
National Institutes of Health.
[FR Doc. E6–14191 Filed 8–25–06; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
mstockstill on PROD1PC61 with NOTICES
National Institutes of Health
Government-Owned Inventions;
Availability for Licensing
National Institutes of Health,
Public Health Service, HHS.
ACTION: Notice.
AGENCY:
VerDate Aug<31>2005
15:09 Aug 25, 2006
Jkt 208001
SUMMARY: The inventions listed below
are owned by an agency of the U.S.
Government and are available for
licensing in the U.S. in accordance with
35 U.S.C. 207 to achieve expeditious
commercialization of results of
federally-funded research and
development. Foreign patent
applications are filed on selected
inventions to extend market coverage
for companies and may also be available
for licensing.
ADDRESSES: Licensing information and
copies of the U.S. patent applications
listed below may be obtained by writing
to the indicated licensing contact at the
Office of Technology Transfer, National
Institutes of Health, 6011 Executive
Boulevard, Suite 325, Rockville,
Maryland 20852–3804; telephone: 301/
496–7057; fax: 301/402–0220. A signed
Confidential Disclosure Agreement will
be required to receive copies of the
patent applications.
Diagnostic and Therapeutic Strategies
for Metastatic Hepatocellular
Carcinoma by Targeting Osteopontin
Description of Technology: Cancer is
one of the leading causes of death in
United States and it is estimated that
there will be more than half a million
deaths caused by cancer in 2006. For the
last decade breast and prostate cancer
survival rate has significantly decreased
thanks to contribution of screening,
early detection and novel therapeutics.
This success needs to be translated to
other cancers as well, where there is a
need of novel diagnostic and
therapeutic strategies for successful
disease management.
Osteopontin (OPN) is a well known
serum prognostic marker for breast
cancer. This technology identifies a
10kD residue of OPN as a potential
prognostic marker and therapeutic target
for metastatic hepatocellular carcinoma
(HCC). Mechanistically, OPN has been
shown to be a novel substrate for MMP–
9 and the 10kD fragment is
demonstrated to be a mediator of cell
invasion and metastasis. Short synthetic
peptides against OPN have been shown
to block OPN mediated cell invasion,
providing a novel therapeutic approach
targeting OPN. Finally, polyclonal
antibodies against the 10kD fragment of
PO 00000
Frm 00045
Fmt 4703
Sfmt 4703
OPN have been developed that can be
used for detection of OPN in
physiological fluids of HCC patients.
This technology provides a novel
therapeutic and diagnostic strategy for
the management of HCC patients using
OPN.
Development Status: The technology
is in the pre-clinical stage, animal
studies are under way.
Inventors: Vivian A. Takafuji (NCI) et
al.
Relevant Publications:
1. A manuscript relating to this
invention has been submitted for
publication and will be available once
accepted.
2. J Kim, SS Ki, SD Lee, CJ Han, YC
Kim, SH Park, SY Cho, YJ Hong, HY
Park, M Lee, HH Jung, KH Lee, SH
Jeong. Elevated plasma osteopontin
levels in patients with hepatocellular
carcinoma. Am J Gastroenterol. 2006 Jul
18; Epub ahead of print, doi: 10.1111/
j.1572–0241.2006.00679.
3. QH Ye, LX Qin, M Forgues, P He,
JW Kim, AC Peng, R Simon, Y Li, AI
Robles, Y Chen, ZC Ma, ZQ Wu, SL Ye,
YK Liu, ZY Tang, XW Wang. Predicting
hepatitis B virus-positive metastatic
hepatocellular carcinomas using gene
expression profiling and supervised
machine learning. Nat Med. 2003 Apr;
9(4):416–423.
Patent Status: U.S. Provisional
Application No. 60/805,298 filed 20 Jun
2006 (HHS Reference No. E–201–2006/
0–US–01).
Licensing Status: This technology is
available for licensing under an
exclusive or non-exclusive patent
license.
Licensing Contact: Michelle Booden,
Ph.D.; 301/451–7337;
boodenm@mail.nih.gov.
Collaborative Research Opportunity:
The NCI Laboratory of Human
Carcinogenesis is seeking statements of
capability or interest from parties
interested in collaborative research to
further develop, evaluate, or
commercialize diagnostic and
therapeutic strategies for metastatic
hepatocellular carcinoma. Please
contact Betty Tong at 301–594–4263 or
tongb@mail.nih.gov for more
information.
E:\FR\FM\28AUN1.SGM
28AUN1
Federal Register / Vol. 71, No. 166 / Monday, August 28, 2006 / Notices
mstockstill on PROD1PC61 with NOTICES
Hybrid T-Cell Receptors for the
Development of Improved Vaccines
Description of Technology: Cancer is
one of the leading causes of death in
United States and it is estimated that
there will be more than half a million
deaths caused by cancer in 2006. A
major drawback of the current
chemotherapy-based therapeutics is the
cytotoxic side-effects associated with
them. Thus there is a dire need to
develop new therapeutic strategies with
fewer side-effects. Immuno-therapy has
taken a lead among the new cancer
therapeutic approaches. Adoptive
immunotherapy is one of the most
promising new therapeutic approaches
that enhance the innate immunity of an
individual to fight against a certain
disease.
T cell receptors (TCR) are the proteins
responsible for the T cell’s ability to
recognize infected or transformed cells.
TCR consists of two domains, one
variable domain that recognizes the
antigen and one constant region that
helps the TCR anchor to the membrane
and transmit the recognition signal by
interacting with other proteins.
The present invention involves the
construction of hybrid anti-cancer TCR
that is half mouse and half human.
Functional analysis reveals that human
TCR with a mouse constant region is
significantly better than pure human
TCR. This hybrid protein when put into
human T cells makes these cells much
better in recognizing cancer associated
proteins. The hybrid protein can be
used to improve the function of a T cell
providing diagnostic and therapeutic
applications in cancer and infectious
diseases.
Development Status: The technology
is in the pre-clinical stage, animal
studies are complete, and a clinical
protocol for a Phase I clinical trial for
stage IV refractory melanoma is
currently under review by the NIH IRB.
Inventors: Richard A. Morgan, Cyrille
J. Cohen, Steven A. Rosenberg (NCI).
Patent Status: U.S. Provisional
Application No. 60/796,853 filed 03
May 2006 (HHS Reference No. E–086–
2006/0–US–01).
Relevant Publications:
1. CJ Cohen, Y Zhao, Z Zheng, SA
Rosenberg, RA Morgan. Enhanced
antitumor activity of murine-human
hybrid T-cell receptor (TCR) in human
lymphocytes is associated with
improved pairing and TCR/CD3
stability. Cancer Res., in press.
2. MS Hughes, YY Yu, ME Dudley, Z
Zheng, PF Robbins, Y Li, J Wunderlich,
RG Hawley, M Moayeri, SA Rosenberg,
RA Morgan. Transfer of a TCR gene
derived from a patient with a marked
VerDate Aug<31>2005
15:09 Aug 25, 2006
Jkt 208001
antitumor response conveys highly
active T-cell effector functions. Hum
Gene Ther. 2005 Apr;16(4):457–472.
Licensing Status: This technology is
available for licensing under an
exclusive or non-exclusive patent
license.
Licensing Contact: Michelle Booden,
Ph.D.; 301/451–7337;
boodenm@mail.nih.gov
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 hybrid T-cell receptors
for the development of improved
vaccines. Please contact Betty Tong at
301–496–0477; tongb@mail.nih.gov for
more information.
Adoptive Immunotherapy With T
Lymphocytes Engineered for Enhanced
Survival
Description of Technology: Available
for licensing is a composition,
comprising genetically engineered
lymphocytes, transduced to express
elevated levels of cytokine proteins.
This technology is useful for improving
cellular adoptive immunotherapies to
treat a range of infectious diseases and
cancers.
Adoptive immunotherapy has
repeatedly been shown to be useful in
the treatment of patients with metastatic
melanoma. However, clinical efficacy of
this treatment is limited by the shortlived survival of the transferred,
autologous, antigen-specific T cells. It
would be desirable to genetically
modify effector cells to provide not only
enhanced effector cell survival, but also
desired antigen specificity, and
improved function, and safety. The
current technology provides a method
address this desire, by genetically
modifying lymphocytes using retroviral
vectors.
Specifically, isolated autologous T
lymphocytes can be transformed with
polynucleotides encoding endogenous
cytokines, for example IL–7 or IL–15.
IL–15-transduced lymphocyte cultures
demonstrate prolonged in vitro
persistence. In addition, T cells can be
transduced to express not only
cytokines but also T cell receptors to
confer specificity for certain antigens.
Recent data showed that human T
lymphocytes engineered to express a
murine anti-human p53 T cell receptor
can recognize tumor cell lines, as well
as fresh human tumors, and are able to
kill p53-expressing human tumor cells.
Also provided in the invention are
methods for treating patients with
transformed lymphocytes as part of
adoptive immunotherapy. Applications
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50927
of this technology beyond cancer
include the potential use of cytokine
expressing cells in treating infectious
and autoimmune diseases and
vaccination.
Inventors: Steven A. Rosenberg et al.
(NCI).
Publications:
1. L Gattinoni, SE Finkelstein, CA
Klebanoff, PA Antony, DC Palmer, PJ
Spiess, LN Hwang, Z Yu, C Wrzesinski,
DM Heimann, CD Surh, SA Rosenberg,
NP Restifo. Removal of homeostatic
cytokine sinks by lymphodepletion
enhances the efficacy of adoptively
transferred tumor-specific CD8+ T cells.
J Exp Med. 2005 Oct 3;202(7):907–912.
2. LX Wang, R Li, G Yang, M Lim, A
O’Hara, Y Chu, BA Fox, NP Restifo, WJ
Urba, HM Hu. Interleukin-7-dependent
expansion and persistence of
melanoma-specific T cells in
lymphodepleted mice lead to tumor
regression and editing. Cancer Res. 2005
Nov 15;65(22):10569–10577.
3. L Gattinoni, DJ Powell Jr, SA
Rosenberg, NP Restifo. Adoptive
immunotherapy for cancer: building on
success. Nat Rev Immunol. 2006
May;6(5):383–393.
4. CJ Cohen, et al. Recognition of fresh
human tumor by human peripheral
blood lymphocytes transduced with a
bicistronic retroviral vector encoding a
murine anti-p53 TCR. J Immunol. 2005
Nov 1;175(9):5799–5808.
5. C Hsu, et al. Primary human T
lymphocytes engineered with a codonoptimized IL–15 gene resist cytokine
withdrawal-induced apoptosis and
persist long-term in the absence of
exogenous cytokine. J Immunol. 2005
Dec 1;175(11):7226–7234.
6. 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.
7. CA Klebanoff, et al. IL–15 enhances
the in vivo antitumor activity of tumorreactive CD8+ T cells. Proc Natl Acad
Sci USA 2004 Feb 17;101(7):1969–1974.
8. K Liu and SA Rosenberg.
Interleukin-2-independent proliferation
of human melanoma-reactive T
lymphocytes transduced with an
exogenous IL–2 gene is stimulation
dependent. J Immunother. 2003 MayJun;26(3):190–201.
9. K Liu and SA Rosenberg.
Transduction of an IL–2 gene into
human melanoma-reactive lymphocytes
results in their continued growth in the
absence of exogenous IL–2 and
maintenance of specific antitumor
activity. J Immunol. 2001
Dec1;167(11):6356–6365.
E:\FR\FM\28AUN1.SGM
28AUN1
50928
Federal Register / Vol. 71, No. 166 / Monday, August 28, 2006 / Notices
Patent Status: U.S. Provisional
Application No. 60/617,340 filed 08 Oct
2004 (HHS Reference No. E–340–2004/
0-US–01); PCT Application No. PCT/
US05/3640 filed 07 Oct 2005 (HHS
Reference No. E–340–2004/2-PCT–01)
Licensing Status: Available for
exclusive and non-exclusive licensing.
Licensing Contact: Michelle A.
Booden, Ph.D.; 301/451–7337;
boodenm@mail.nih.gov
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 the clinical applications
of T cell receptor technology. Please
contact Steven A. Rosenberg, M.D.,
Ph.D. at 301–496–4164 for more
information.
Dated: August 21, 2006.
Steven M. Ferguson,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. E6–14184 Filed 8–25–06; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
National Cancer Institute; Notice of
Closed Meeting
mstockstill on PROD1PC61 with NOTICES
Pursuant to section 10(d) of the
Federal Advisory Committee Act, as
amended (5 U.S.C. Appendix 2), notice
is hereby given of the following
meeting.
The meeting will be closed to the
public in accordance with the
provisions set forth in sections
552b(c)(4) and 552b(c)(6), Title 5 U.S.C.,
as amended. The grant applications and
the discussions could disclose
confidential trade secrets or commercial
property such as patentable material,
and personal information concerning
individuals associated with the grant
applications, the disclosure of which
would constitute a clearly unwarranted
invasion of personal privacy.
Name of Committee: National Cancer
Institute Special Emphasis Panel, CA07–002,
008, 009, Application of Emerging
Technologies for Cancer Research (STTR
R41/R42), (SBIR R43/44), (R21/R33, R21,
R33).
Date: October 18–19, 2006.
Time: 8 a.m. to 5 p.m.
Agenda: To review and evaluate grant
applications.
Place: Marriott Bethesda Suites, 6711
Democracy Boulevard, Bethesda, MD 20817.
Contact Person: C. Michael Kerwin, PhD,
MPH, Scientific Review Administrator,
VerDate Aug<31>2005
15:09 Aug 25, 2006
Jkt 208001
Special Review and Logistics Branch,
Division of Extramural Activities, National
Cancer Institute, NIH, 6116 Executive Blvd.,
Rm. 8057, Bethesda, MD 20892–8329. 301–
496–7421. kerwinm@mail.nih.gov.
(Catalogue of Federal Domestic Assistance
Program Nos. 93.392, Cancer Construction;
93.393, Cancer Cause and Prevention
Research; 93.394, Cancer Detection and
Diagnosis Research; 93.395, Cancer
Treatment Research; 93.396, Cancer Biology
Research; 93.397, Cancer Centers Support;
93.398, Cancer Research Manpower; 93.399,
Cancer Control, National Institutes of Health,
HHS).
Dated: August 17, 2006.
Anna Snouffer,
Acting Director, Office of Federal Advisory
Committee Policy.
[FR Doc. 06–7167 Filed 8–25–06; 8:45 am]
BILLING CODE 4140–01–M
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
National Institute of Dental &
Craniofacial Research; Notice of
Closed Meetings
Pursuant to section 10(d) of the
Federal Advisory Committee Act, as
amended (5 U.S.C. Appendix 2), notice
is hereby given of the following
meetings.
The meetings will be closed to the
public in accordance with the
provisions set forth in sections
552b(c)(4) and 552b(c)(6), Title 5 U.S.C.,
as amended. The grant applications and
the discussions could disclose
confidential trade secrets or commercial
property such as patentable material,
and personal information concerning
individuals associated with the grant
applications, the disclosure of which
would constitute a clearly unwarranted
invasion of personal privacy.
Name of Committee: National Institute of
Dental and Craniofacial Research Special
Emphasis Panel; 07–07, Review R21.
Date: September 28, 2006.
Time: 11:30 a.m. to 12:30 p.m.
Agenda: To review and evaluate grant
applications.
Place: National Institutes of Health,
Natcher Building, 45 Center Drive, Bethesda,
MD 20892. (Telephone Conference Call).
Contact Person: Raj K. Krishnaraju, PhD,
MS, Scientific Review Administrator,
Scientific Review Branch, National Inst of
Dental & Craniofacial Research, National
Institutes of Health, 45 Center Dr., Rm 4AN
32J, Bethesda, MD 20892. 301–594–4864.
kkrishna@nidcr.nih.gov.
Name of Committee: National Institute of
Dental and Craniofacial Research Special
Emphasis Panel; 07–06, Review R03s, Ks.
Date: October 19, 2006.
Time: 10:30 a.m. to 1:30 p.m.
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Agenda: To review and evaluate grant
applications.
Place: National Institutes of Health,
Natcher Building, 45 Center Drive, Bethesda,
MD 20892. (Telephone Conference Call).
Contact Person: Raj K. Krishnaraju, PhD,
MS, Scientific Review Administrator,
Scientific Review Branch, National Inst of
Dental & Craniofacial Research, National
Institutes of Health, 45 Center Dr., Rm 4AN
32J, Bethesda, MD 20892. 301–594–4864.
kkrishna@nidcr.nih.gov.
Name of Committee: National Institute of
Dental and Craniofacial Research Special
Emphasis Panel; 07–17, Review R01.
Date: October 19, 2006.
Time: 2 p.m. to 3 p.m.
Agenda: To review and evaluate grant
applications.
Place: National Institutes of Health,
Natcher Building, 45 Center Drive, Bethesda,
MD 20892. (Telephone Conference Call).
Contact Person: Sooyoun (Sonia) Kim, MS,
45 Center Dr., 4An 32B, Division of
Extramural Research, National Inst. of Dental
& Craniofacial Research, National Institutes
of Health, Bethesda, MD 20892. (301) 594–
4827. kims@email.nidr.nih.gov.
Name of Committee: National Institute of
Dental and Craniofacial Research Special
Emphasis Panel; 07–08, Review of R21s.
Date: November 10, 2006.
Time: 2 p.m. to 3:30 p.m.
Agenda: To review and evaluate grant
applications.
Place: National Institutes of Health,
Natcher Building, 45 Center Drive, Bethesda,
MD 20892. (Telephone Conference Call).
Contact Person: Yujing Liu, MD, PhD,
Scientific Review Administrator, National
Institute of Dental & Craniofacial Res., 45
Center Drive, Natcher Building, Rm. 4AN38E,
Bethesda, MD 20892. (301) 594–3169.
yujing_liu@nih.gov.
Name of Committee: National Institute of
Dental and Craniofacial Research Special
Emphasis Panel; 07–14, Review of R21.
Date: November 10, 2006.
Time: 3:30 p.m. to 4:30 p.m.
Agenda: To review and evaluate grant
applications.
Place: National Institutes of Health,
Natcher Building, 45 Center Drive, Bethesda,
MD 20892. (Telephone Conference Call).
Contact Person: Yujing Liu, MD, PhD,
Scientific Review Administrator, National
Institute of Dental & Craniofacial Res., 45
Center Drive, Natcher Building, Rm. 4AN38E,
Bethesda, MD 20892. (301) 594–3169.
yujing_liu@nih.gov.
Name of Committee: National Institute of
Dental and Craniofacial Research Special
Emphasis Panel; 07–09, Review R21s.
Date: November 21, 2006.
Time: 2 p.m. to 3:30 p.m.
Agenda: To review and evaluate grant
applications.
Place: National Institutes of Health,
Natcher Building, 45 Center Drive, Bethesda,
MD 20892. (Telephone Conference Call).
Contact Person: Yujing Liu, MD, PhD,
Scientific Review Administrator, National
Institute of Dental & Craniofacial Res., 45
Center Drive, Natcher Building, Rm. 4AN38E,
Bethesda, MD 20892. (301) 594–3169.
yujing_liu@nih.gov.
E:\FR\FM\28AUN1.SGM
28AUN1
]]>Agencies
[Federal Register Volume 71, Number 166 (Monday, August 28, 2006)]
[Notices]
[Pages 50926-50928]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E6-14184]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions; Availability for Licensing
AGENCY: National Institutes of Health, Public Health Service, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The inventions listed below are owned by an agency of the U.S.
Government and are available for licensing in the U.S. in accordance
with 35 U.S.C. 207 to achieve expeditious commercialization of results
of federally-funded research and development. Foreign patent
applications are filed on selected inventions to extend market coverage
for companies and may also be available for licensing.
ADDRESSES: Licensing information and copies of the U.S. patent
applications listed below may be obtained by writing to the indicated
licensing contact at the Office of Technology Transfer, National
Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville,
Maryland 20852-3804; telephone: 301/496-7057; fax: 301/402-0220. A
signed Confidential Disclosure Agreement will be required to receive
copies of the patent applications.
Diagnostic and Therapeutic Strategies for Metastatic Hepatocellular
Carcinoma by Targeting Osteopontin
Description of Technology: Cancer is one of the leading causes of
death in United States and it is estimated that there will be more than
half a million deaths caused by cancer in 2006. For the last decade
breast and prostate cancer survival rate has significantly decreased
thanks to contribution of screening, early detection and novel
therapeutics. This success needs to be translated to other cancers as
well, where there is a need of novel diagnostic and therapeutic
strategies for successful disease management.
Osteopontin (OPN) is a well known serum prognostic marker for
breast cancer. This technology identifies a 10kD residue of OPN as a
potential prognostic marker and therapeutic target for metastatic
hepatocellular carcinoma (HCC). Mechanistically, OPN has been shown to
be a novel substrate for MMP-9 and the 10kD fragment is demonstrated to
be a mediator of cell invasion and metastasis. Short synthetic peptides
against OPN have been shown to block OPN mediated cell invasion,
providing a novel therapeutic approach targeting OPN. Finally,
polyclonal antibodies against the 10kD fragment of OPN have been
developed that can be used for detection of OPN in physiological fluids
of HCC patients. This technology provides a novel therapeutic and
diagnostic strategy for the management of HCC patients using OPN.
Development Status: The technology is in the pre-clinical stage,
animal studies are under way.
Inventors: Vivian A. Takafuji (NCI) et al.
Relevant Publications:
1. A manuscript relating to this invention has been submitted for
publication and will be available once accepted.
2. J Kim, SS Ki, SD Lee, CJ Han, YC Kim, SH Park, SY Cho, YJ Hong,
HY Park, M Lee, HH Jung, KH Lee, SH Jeong. Elevated plasma osteopontin
levels in patients with hepatocellular carcinoma. Am J Gastroenterol.
2006 Jul 18; Epub ahead of print, doi: 10.1111/j.1572-0241.2006.00679.
3. QH Ye, LX Qin, M Forgues, P He, JW Kim, AC Peng, R Simon, Y Li,
AI Robles, Y Chen, ZC Ma, ZQ Wu, SL Ye, YK Liu, ZY Tang, XW Wang.
Predicting hepatitis B virus-positive metastatic hepatocellular
carcinomas using gene expression profiling and supervised machine
learning. Nat Med. 2003 Apr; 9(4):416-423.
Patent Status: U.S. Provisional Application No. 60/805,298 filed 20
Jun 2006 (HHS Reference No. E-201-2006/0-US-01).
Licensing Status: This technology is available for licensing under
an exclusive or non-exclusive patent license.
Licensing Contact: Michelle Booden, Ph.D.; 301/451-7337;
boodenm@mail.nih.gov.
Collaborative Research Opportunity: The NCI Laboratory of Human
Carcinogenesis is seeking statements of capability or interest from
parties interested in collaborative research to further develop,
evaluate, or commercialize diagnostic and therapeutic strategies for
metastatic hepatocellular carcinoma. Please contact Betty Tong at 301-
594-4263 or tongb@mail.nih.gov for more information.
[[Page 50927]]
Hybrid T-Cell Receptors for the Development of Improved Vaccines
Description of Technology: Cancer is one of the leading causes of
death in United States and it is estimated that there will be more than
half a million deaths caused by cancer in 2006. A major drawback of the
current chemotherapy-based therapeutics is the cytotoxic side-effects
associated with them. Thus there is a dire need to develop new
therapeutic strategies with fewer side-effects. Immuno-therapy has
taken a lead among the new cancer therapeutic approaches. Adoptive
immunotherapy is one of the most promising new therapeutic approaches
that enhance the innate immunity of an individual to fight against a
certain disease.
T cell receptors (TCR) are the proteins responsible for the T
cell's ability to recognize infected or transformed cells. TCR consists
of two domains, one variable domain that recognizes the antigen and one
constant region that helps the TCR anchor to the membrane and transmit
the recognition signal by interacting with other proteins.
The present invention involves the construction of hybrid anti-
cancer TCR that is half mouse and half human. Functional analysis
reveals that human TCR with a mouse constant region is significantly
better than pure human TCR. This hybrid protein when put into human T
cells makes these cells much better in recognizing cancer associated
proteins. The hybrid protein can be used to improve the function of a T
cell providing diagnostic and therapeutic applications in cancer and
infectious diseases.
Development Status: The technology is in the pre-clinical stage,
animal studies are complete, and a clinical protocol for a Phase I
clinical trial for stage IV refractory melanoma is currently under
review by the NIH IRB.
Inventors: Richard A. Morgan, Cyrille J. Cohen, Steven A. Rosenberg
(NCI).
Patent Status: U.S. Provisional Application No. 60/796,853 filed 03
May 2006 (HHS Reference No. E-086-2006/0-US-01).
Relevant Publications:
1. CJ Cohen, Y Zhao, Z Zheng, SA Rosenberg, RA Morgan. Enhanced
antitumor activity of murine-human hybrid T-cell receptor (TCR) in
human lymphocytes is associated with improved pairing and TCR/CD3
stability. Cancer Res., in press.
2. MS Hughes, YY Yu, ME Dudley, Z Zheng, PF Robbins, Y Li, J
Wunderlich, RG Hawley, M Moayeri, SA Rosenberg, RA Morgan. Transfer of
a TCR gene derived from a patient with a marked antitumor response
conveys highly active T-cell effector functions. Hum Gene Ther. 2005
Apr;16(4):457-472.
Licensing Status: This technology is available for licensing under
an exclusive or non-exclusive patent license.
Licensing Contact: Michelle Booden, Ph.D.; 301/451-7337;
boodenm@mail.nih.gov
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
hybrid T-cell receptors for the development of improved vaccines.
Please contact Betty Tong at 301-496-0477; tongb@mail.nih.gov for more
information.
Adoptive Immunotherapy With T Lymphocytes Engineered for Enhanced
Survival
Description of Technology: Available for licensing is a
composition, comprising genetically engineered lymphocytes, transduced
to express elevated levels of cytokine proteins. This technology is
useful for improving cellular adoptive immunotherapies to treat a range
of infectious diseases and cancers.
Adoptive immunotherapy has repeatedly been shown to be useful in
the treatment of patients with metastatic melanoma. However, clinical
efficacy of this treatment is limited by the short-lived survival of
the transferred, autologous, antigen-specific T cells. It would be
desirable to genetically modify effector cells to provide not only
enhanced effector cell survival, but also desired antigen specificity,
and improved function, and safety. The current technology provides a
method address this desire, by genetically modifying lymphocytes using
retroviral vectors.
Specifically, isolated autologous T lymphocytes can be transformed
with polynucleotides encoding endogenous cytokines, for example IL-7 or
IL-15. IL-15-transduced lymphocyte cultures demonstrate prolonged in
vitro persistence. In addition, T cells can be transduced to express
not only cytokines but also T cell receptors to confer specificity for
certain antigens. Recent data showed that human T lymphocytes
engineered to express a murine anti-human p53 T cell receptor can
recognize tumor cell lines, as well as fresh human tumors, and are able
to kill p53-expressing human tumor cells.
Also provided in the invention are methods for treating patients
with transformed lymphocytes as part of adoptive immunotherapy.
Applications of this technology beyond cancer include the potential use
of cytokine expressing cells in treating infectious and autoimmune
diseases and vaccination.
Inventors: Steven A. Rosenberg et al. (NCI).
Publications:
1. L Gattinoni, SE Finkelstein, CA Klebanoff, PA Antony, DC Palmer,
PJ Spiess, LN Hwang, Z Yu, C Wrzesinski, DM Heimann, CD Surh, SA
Rosenberg, NP Restifo. Removal of homeostatic cytokine sinks by
lymphodepletion enhances the efficacy of adoptively transferred tumor-
specific CD8+ T cells. J Exp Med. 2005 Oct 3;202(7):907-912.
2. LX Wang, R Li, G Yang, M Lim, A O'Hara, Y Chu, BA Fox, NP
Restifo, WJ Urba, HM Hu. Interleukin-7-dependent expansion and
persistence of melanoma-specific T cells in lymphodepleted mice lead to
tumor regression and editing. Cancer Res. 2005 Nov 15;65(22):10569-
10577.
3. L Gattinoni, DJ Powell Jr, SA Rosenberg, NP Restifo. Adoptive
immunotherapy for cancer: building on success. Nat Rev Immunol. 2006
May;6(5):383-393.
4. CJ Cohen, et al. Recognition of fresh human tumor by human
peripheral blood lymphocytes transduced with a bicistronic retroviral
vector encoding a murine anti-p53 TCR. J Immunol. 2005 Nov
1;175(9):5799-5808.
5. C Hsu, et al. Primary human T lymphocytes engineered with a
codon-optimized IL-15 gene resist cytokine withdrawal-induced apoptosis
and persist long-term in the absence of exogenous cytokine. J Immunol.
2005 Dec 1;175(11):7226-7234.
6. 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.
7. CA Klebanoff, et al. IL-15 enhances the in vivo antitumor
activity of tumor-reactive CD8+ T cells. Proc Natl Acad Sci USA 2004
Feb 17;101(7):1969-1974.
8. K Liu and SA Rosenberg. Interleukin-2-independent proliferation
of human melanoma-reactive T lymphocytes transduced with an exogenous
IL-2 gene is stimulation dependent. J Immunother. 2003 May-
Jun;26(3):190-201.
9. K Liu and SA Rosenberg. Transduction of an IL-2 gene into human
melanoma-reactive lymphocytes results in their continued growth in the
absence of exogenous IL-2 and maintenance of specific antitumor
activity. J Immunol. 2001 Dec1;167(11):6356-6365.
[[Page 50928]]
Patent Status: U.S. Provisional Application No. 60/617,340 filed 08
Oct 2004 (HHS Reference No. E-340-2004/0-US-01); PCT Application No.
PCT/US05/3640 filed 07 Oct 2005 (HHS Reference No. E-340-2004/2-PCT-01)
Licensing Status: Available for exclusive and non-exclusive
licensing.
Licensing Contact: Michelle A. Booden, Ph.D.; 301/451-7337;
boodenm@mail.nih.gov
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
the clinical applications of T cell receptor technology. Please contact
Steven A. Rosenberg, M.D., Ph.D. at 301-496-4164 for more information.
Dated: August 21, 2006.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. E6-14184 Filed 8-25-06; 8:45 am]
BILLING CODE 4140-01-P
