Government-Owned Inventions; Availability for Licensing, 58293-58295 [E9-27199]
Download as PDF
<![CDATA[
Federal Register / Vol. 74, No. 217 / Thursday, November 12, 2009 / Notices
A. Background
GSA Bulletin FMR B–12 was signed
on January 18, 2006, and became
effective on May 25, 2006. The Bulletin
provided a list of agencies for which
GSA granted unlimited exemptions
from the display of U.S. Government
license plates and motor vehicle
identification. 41 CFR part 102–34 was
amended on March 20, 2009 (74 FR
11870). It revised the unlimited
exemption from the requirement to
display motor vehicle identification to
exempt motor vehicles used primarily
for investigative, law enforcement,
intelligence, or security duties. The
change recognizes the need for
protecting agency missions and
occupant safety and reduces the
administrative burden of processing
exemptions while maintaining the
objective that Federal motor vehicles are
required to be conspicuously identified
unless exempted (see 40 U.S.C. 609).
Therefore, GSA is canceling this
Bulletin as unlimited exemptions are
covered in 41 CFR 102–34.175.
organizations in order to: Identify best
practices and successful modes of delivering
social services; evaluate the need for
improvements in the implementation and
coordination of public policies relating to
faith- based and other neighborhood
organizations; and make recommendations
for changes in policies, programs, and
practices.
Contact Person for Additional Information:
Mara Vanderslice, 202–260–1931,
mara.vanderslice@hhs.gov.
Supplementary Information: Please contact
Mara Vanderslice for more information about
how to join via conference call line.
Agenda: Topics to be discussed include
deliberation on draft recommendations for
Council report.
B. Procedures
Bulletins regarding motor vehicle
management are located on the Internet
at https://www.gsa.gov/fmrbulletin as
Federal Management Regulation (FMR)
bulletins.
Government-Owned Inventions;
Availability for Licensing
Dated: November 4, 2009.
James Vogelsinger,
Director, Motor Vehicle Management Policy.
[FR Doc. E9–27163 Filed 11–10–09; 8:45 am]
BILLING CODE 6820–14–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
President’s Advisory Council for Faithbased and Neighborhood Partnerships
jlentini on DSKJ8SOYB1PROD with NOTICES
In accordance with section 10(a)(2) of
the Federal Advisory Committee Act
(Pub. L. 92–463), the President’s
Advisory Council for Faith-based and
Neighborhood Partnerships announces
the following meetings:
Name: President’s Advisory Council for
Faith-based and Neighborhood Partnerships
Council Meetings.
Times and Dates:
Tuesday, November 17th, 4 p.m. Eastern.
Tuesday, December 15th, 4 p.m. Eastern.
Tuesday, January 19th, 4 p.m. Eastern.
Place: Meetings will by conference call.
Please RSVP to receive the call-in
information.
Status: Open to the public, limited only by
the space available. Conference call line will
be available.
Purpose: The Council brings together
leaders and experts in fields related to the
work of faith-based and neighborhood
VerDate Nov<24>2008
16:12 Nov 10, 2009
Jkt 220001
Dated: November 1, 2009.
Mara Vanderslice,
Special Assistant.
[FR Doc. E9–27097 Filed 11–10–09; 8:45 am]
BILLING CODE 4154–07–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
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.
Simpler Is Better: The Production of
Young Cell Cultures From Tumor
Infiltrating Lymphocytes (TIL) Yields
More Effective Adoptive Cell Transfer
(ACT) Immunotherapies
Description of Technology: Available
for licensing is an improved method of
adoptive cell transfer (ACT)
immunotherapy that can be utilized to
PO 00000
Frm 00055
Fmt 4703
Sfmt 4703
58293
treat a variety of infectious diseases and
cancers, most notably melanoma.
At its foundation, ACT involves
isolating lymphocytes with high affinity
for a particular antigen, expanding those
cells in vitro to produce a greater
quantity of reactive cells, and infusing
the product cells into patients to attack
cells expressing the antigen, such as
tumor cells, bacterial cells, or viral
particles. Previously utilized ACT
procedures have been plagued by
technical, regulatory, and logistical
problems that have prevented
consistently successful clinical
outcomes. Through years of research,
scientists at the National Institutes of
Health (NIH) have made great strides in
developing ACT into a viable approach
to treat cancer patients. Of note, the
ACT protocols developed by NIH
scientists have successfully treated
patients with refractory metastatic
melanoma who started with very few
effective treatment options. These NIH
scientists have found that isolating cells
from the tumor infiltrating lymphocytes
(TIL) of a patient tumor sample provides
a suitable initial lymphocyte culture for
further in vitro manipulations. They
have also discovered that taking the
isolated cells through one cycle of rapid
expansion (including exposure to IL–2),
rather than multiple cycles, yields
lymphocyte cultures with higher affinity
and longer persistence in patients. Also,
they have found that administering
nonmyeloablative lymphodepleting
chemotherapy prior to the reinfusion of
lymphocytes creates a more favorable
environment within patients for the
transferred cells to execute target cell
killing. These scientists envision that,
for an ACT immunotherapy to gain
regulatory approval and successfully
treat a wide array of patients, it will
need to be rapid, reliable, and
technically simple. One of the most
critical factors to this approach is the
generation of effective lymphocyte
cultures that will rapidly and repeatedly
attack the target cells when infused into
patients.
Scientists at the NIH have developed
a method of generating CD8+ selected
‘‘young’’ lymphocyte cultures for
infusion into cancer patients.
Lymphocytes that spend fewer days in
vitro between their initial isolation from
TIL and their ultimate reinfusion into
patients compared to lymphocytes
cultured by previous ACT protocols are
considered young lymphocyte cultures.
Young lymphocytes, typically 19–35
days old when reinfused into patients,
exhibit improved proliferation, survival,
and enhanced anti-tumor activity within
patients to yield greater tumor
regression compared to older
E:\FR\FM\12NON1.SGM
12NON1
jlentini on DSKJ8SOYB1PROD with NOTICES
58294
Federal Register / Vol. 74, No. 217 / Thursday, November 12, 2009 / Notices
lymphocytes, typically 44+ days old.
Furthermore, the generation of young
lymphocyte cultures is more rapid,
reliable, and technically easier than
previous ACT culturing methods. Young
lymphocytes are isolated from TIL,
directed against a single isolated tumor
cell suspension, enriched for CD8
expression, and rapidly expanded once
using autologous feeder cells without
testing the culture for antigen
specificity.
This approach to ACT offers a
potentially significant improvement and
a valuable new immunotherapeutic tool
for attacking tumors many types of
tumors. For diseases, such as metastatic
melanoma, where patients may only
have weeks or months of life
expectancy, this technology, which
provides for improved cell cultures
prepared in less time, can make a
difference between life and death. 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.
Applications:
• An improved immunotherapy
methodology to treat and/or prevent the
recurrence of a variety of human
cancers, such as melanomas and
glioblastomas, infectious diseases, and
autoimmune diseases by transferring
young lymphocyte cultures engineered
into cancer patients.
• A technically simpler, more rapid,
more clinically reliable ACT procedure
with greater potential to overcome the
technical, regulatory, and logistical
hurdles of past ACT methods. This
technology could be broadly
transferrable to a wide array of
institutions to treat a wide array of
patients.
• The immunotherapy component of
a combination therapy regimen aimed at
targeting the specific tumor-associated
antigens expressed by the cancer cells of
individual patients.
Advantages:
• Technically simpler than previous
ACT methods: Decreased number of
steps in the procedure and less analysis
of the cell cultures prior to reinfusion
into patients.
• More rapid than previous ACT
methods: Adoptively transferred
lymphocytes spend fewer days
undergoing in vitro culturing, so they
are introduced to patients with
potentially short life expectancies more
quickly.
• Reliable, life-saving technology:
This technology is anticipated by the
inventors to yield greater tumor
regression and more objective clinical
VerDate Nov<24>2008
16:12 Nov 10, 2009
Jkt 220001
responses in patients compared to
previous ACT protocols and all
previously attempted treatments for
metastatic melanoma.
Development Status: This technology
is being utilized in a clinical protocol
for adoptive cell transfer. The
technology is a critical component of
the successful immunotherapy regimen
being used by the inventors and other
clinicians at the NCI. Patients enrolled
in ACT protocols are expected to show
enhanced tumor regression and more
objective responses compared to results
obtained with previous protocols.
Market: Cancer continues to be a
medical and financial burden on U.S.
public health. According to U.S.
estimates, cancer is the second leading
cause of death with over 565,000 deaths
reported in 2008 and almost 1.5 million
new cases were reported (excluding
some skin cancers) in 2008. In 2007, the
NIH estimated that the overall cost of
cancer was $219.2 billion dollars and
$89 billion went to direct medical costs.
Despite our increasing knowledge of
oncology and cancer treatment methods,
the fight against cancer will continue to
benefit from the development of new
therapeutics aimed at treating
individual patients.
Inventors: Mark E. Dudley and Steven
A. Rosenberg (NCI).
Related Publications:
1. KQ Tran et al. Minimally cultured
tumor-infiltrating lymphocytes display
optimal characteristics for adoptive cell
therapy. J Immunother. 2008
Oct;31(8):742–751.
2. SA Rosenberg and ME Dudley.
Adoptive cell therapy for the treatment
of patients with metastatic melanoma.
Curr Opin Immunol. 2009
Apr;21(2):233–240
Patent Status: HHS Reference No. E–
273–2009/0—U.S. Provisional
Application No. 61/237,889 filed 28
Aug 2009
Related Technologies: HHS Reference
No. E–275–2002/1—U.S. Patent
Application No. 10/526,697 filed 05
May 2005 (foreign counterparts in
Europe, Canada, and Australia)
Licensing Status: Available for
licensing.
Licensing Contact: Samuel E. Bish,
Ph.D.; 301–435–5282;
bishse@mail.nih.gov
Collaborative Research Opportunity:
The Center for Cancer Research, Surgery
Branch, is seeking statements of
capability or interest from parties
interested in collaborative research to
further develop, evaluate, or
commercialize cell and gene therapy
technologies, and personalized
medicines. Please contact John D.
Hewes, Ph.D. at 301–435–3121 or
PO 00000
Frm 00056
Fmt 4703
Sfmt 4703
hewesj@mail.nih.gov for more
information.
Treating Cancer With Anti-Angiogenic
Chimeric Antigen Receptors
Description of Technology: Metastasis,
the growth and spread of cancer from a
localized tumor to other sites in the
body, is promoted by the formation of
new blood vessels through angiogenesis
to ‘‘feed’’ the tumor. There is an urgent
need to develop new therapeutic
strategies that combine fewer sideeffects and more specific anti-tumor
activity in order to block cancer
metastasis in patients. Adoptive
immunotherapy is a promising new
approach to cancer treatment that
engineers an individual’s innate and
adaptive immune system to fight against
specific diseases, including the spread
of cancer.
Chimeric antigen receptors (CARs) are
hybrid proteins consisting of the portion
of an antibody that recognizes a tumorassociated antigen (TAA) fused to
protein domains that signal to activate
the CAR-expressing cell. Human cells
that express CARs, most notably T cells,
can recognize specific tumor antigens in
an MHC-unrestricted manner with high
reactivity. CARs are able to mediate an
immune response that promotes robust
tumor killing in targeted cells.
Scientists at the National Institutes of
Health (NIH) have developed CARs with
high affinity for the vascular endothelial
growth factor receptor 2 (VEGFR2) (also
known as kinase domain region (KDR)
in humans and fetal liver kinase-1
(Flk-1) in mice) to utilize as an
antiangiogenic tumor therapy. VEGFR2
is expressed on non-cancerous vascular
endothelia cells, but is overexpressed on
tumor endothelial cells in a variety of
cancers, especially solid tumors.
VEGFR2 overexpression promotes
tumor vasculature, growth, and
metastasis. The VEGFR2-specific CARs
feature the antigen binding domain of
the KDR–1121 or DC101 antibody,
which recognize portions of the human
and mouse VEGFR2, respectively. This
antibody component is fused to the
transmembrane and intracellular
signaling domains of a T cell receptor
(TCR). These CARs combine high
affinity recognition of VEGFR2 provided
by the antibody portion with the target
cell killing activity of a cell expressing
an activated TCR. Infusion of these
VEGFR2-specific CARs into patients
could prove to be a powerful new
immunotherapeutic tool for blocking
angiogenic cancer metastasis by killing
VEGFR2+ tumor cells.
Applications:
• Immunotherapeutics to treat and/or
prevent the reoccurrence of a variety of
E:\FR\FM\12NON1.SGM
12NON1
jlentini on DSKJ8SOYB1PROD with NOTICES
Federal Register / Vol. 74, No. 217 / Thursday, November 12, 2009 / Notices
human cancers that overexpress human
VEGFR2 by introducing anti-VEGFR2
CAR expressing T cells into patients
with metastatic cancer.
• A possible prophylactic therapy to
prevent the spread of cancer in patients
whose cancer is predicted to
metastasize.
• A drug component of a combination
immunotherapy regimen aimed at
targeting the specific tumor-associated
antigens expressed by cancer cells
within individual patients.
Advantages:
• This discovery is widely applicable
to many different cancers: VEGFR2 is
overexpressed in many metastatic
cancers that utilize angiogenesis to
spread from their initial site of
development. An immunotherapy
protocol using anti-VEGFR2 CAR could
treat a variety of cancer types.
• Antiangiogenic tumor therapy is
anticipated to generate fewer sideeffects compared to other treatment
approaches: These CARs can be
delivered directly to the bloodstream to
gain easy access to the targeted tumor
vascular endothelial cells with minimal
effects to normal tissues. Furthermore,
destroying tumor blood vessels could
accelerate tumor cell death so that the
therapy can be administered for a
shorter period of time. A reduced
therapeutic timeframe and minimal
access to normal tissues should
contribute to reduced side-effects and
lowered toxicity for this treatment.
• The technology is anticipated to be
highly effective and killing metastatic
cells: Most angiogenic tumor epithelial
cells are believed to overexpress
VEGFR2 to a similar degree.
Administering a therapeutically
effective amount of anti-VEGFR2 CARs
to patients may leave no or little tumor
cells remaining with an opportunity to
metastasize. Many current angiogenesis
therapies do not kill tumors, but rather
stabilize the tumor, so they require long
periods of administration.
Development Status: This technology
could soon be ready for clinical
development since the inventors plan to
initiate clinical trials using CAR
engineered lymphocytes for adoptive
immunotherapy of cancer.
Market: The Food and Drug
Administration (FDA) has approved
eight therapies with antiangiogenic
properties, including Avastin®,
Erbitux®, Vectibix®, Herceptin®,
Tarceva®, Nexavar®, Sutent®,
ToriselTM, Velcade®, and Thalomid®.
The majority of these drugs produced
worldwide sales exceeding an estimated
$500 million in 2007. The fight against
cancer and its spread will continue to
benefit from the development of new
VerDate Nov<24>2008
16:12 Nov 10, 2009
Jkt 220001
therapeutics aimed at treating
individual patients.
Cancer continues to be a medical and
financial burden on U.S. public health.
Statistically, in the U.S. cancer is the
second leading cause of death with over
565,000 deaths reported in 2008 and
almost 1.5 million new cases were
reported (excluding some skin cancers)
in 2008, many with the potential to
metastasize. In 2007, the NIH estimated
that the overall cost of cancer was
$219.2 billion dollars and $89 billion
went to direct medical costs.
Inventors: Steven A. Rosenberg et al.
(NCI).
Patent Status: HHS Reference No. E–
205–2009/0—U.S. Provisional
Application No. 61/247,625 filed 01 Oct
2009.
Related Technologies:
• E–045–2009/0—U.S. Provisional
Application No. 61/154,080 filed 20 Feb
2009
• E–312–2007/1—PCT Application
No. PCT/US2008/077333 filed 23 Sep
2008
• E–059–2007/2—PCT Application
No. PCT/US2008/050841 filed 11 Jan
2008, which published as WO 2008/
089053 on 24 Jul 2008
• E–304–2006/0—U.S. Provisional
Patent Application No. 60/847,447 filed
26 Sep 2006; PCT Application No. PCT/
US2007/079487 filed 26 Sep 2007,
which published as WO 2008/039818
on 03 Apr 2008
• E–093–1995/0—PCT Application
No. PCT/US1996/04143 filed 27 Mar
1996, which published as WO 1996/
30516 on 03 Oct 1996
• E–093–1995/2—U.S. NonProvisional Application No. 08/084,994
filed 02 Jul 1993
Licensing Status: Available for
licensing.
Licensing Contact: Samuel E. Bish,
Ph.D.; 301–435–5282;
bishse@mail.nih.gov.
Collaborative Research Opportunity:
The Center for Cancer Research, Surgery
Branch, is seeking statements of
capability or interest from parties
interested in collaborative research to
further develop, evaluate, or
commercialize this technology. Please
contact John D. Hewes, Ph.D. at 301–
435–3121 or hewesj@mail.nih.gov for
more information.
Dated: November 3, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. E9–27199 Filed 11–10–09; 8:45 am]
BILLING CODE 4140–01–P
PO 00000
Frm 00057
Fmt 4703
Sfmt 4703
58295
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.
A Method of Identifying Cdk5/p35
Modulators, and Possible Diagnostic or
Therapeutic Uses for
Neurodegenerative Diseases
Description of Invention: Cyclindependent kinase 5 (Cdk5) is a serine/
threonine cyclin-dependent kinase that
is highly expressed in the central
nervous system and controls many
biological processes that impact
learning and memory, as well as pain
and drug addiction. Studies have
indicated that abnormal Cdk5 activity
may be associated with the onset of
neurodegenerative diseases, such as
Alzheimer’s disease, Parkinson’s
disease, and amyotrophic lateral
sclerosis (ALS). The kinase activity of
Cdk5 is turned on when it binds to one
of the two proteins considered to be
neuronal activators, p35 and p39.
Scientists at the NIH designed a cellbased assay to screen for p35
transcriptional regulators that work as
upstream regulators of Cdk5. This
technology may be useful for assessing
the presence and risk of conditions
associated with atypical Cdk5 kinase
activity or for finding drug modulators
that could be promising drug targets.
Applications:
E:\FR\FM\12NON1.SGM
12NON1
]]>Agencies
[Federal Register Volume 74, Number 217 (Thursday, November 12, 2009)]
[Notices]
[Pages 58293-58295]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E9-27199]
-----------------------------------------------------------------------
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.
Simpler Is Better: The Production of Young Cell Cultures From Tumor
Infiltrating Lymphocytes (TIL) Yields More Effective Adoptive Cell
Transfer (ACT) Immunotherapies
Description of Technology: Available for licensing is an improved
method of adoptive cell transfer (ACT) immunotherapy that can be
utilized to treat a variety of infectious diseases and cancers, most
notably melanoma.
At its foundation, ACT involves isolating lymphocytes with high
affinity for a particular antigen, expanding those cells in vitro to
produce a greater quantity of reactive cells, and infusing the product
cells into patients to attack cells expressing the antigen, such as
tumor cells, bacterial cells, or viral particles. Previously utilized
ACT procedures have been plagued by technical, regulatory, and
logistical problems that have prevented consistently successful
clinical outcomes. Through years of research, scientists at the
National Institutes of Health (NIH) have made great strides in
developing ACT into a viable approach to treat cancer patients. Of
note, the ACT protocols developed by NIH scientists have successfully
treated patients with refractory metastatic melanoma who started with
very few effective treatment options. These NIH scientists have found
that isolating cells from the tumor infiltrating lymphocytes (TIL) of a
patient tumor sample provides a suitable initial lymphocyte culture for
further in vitro manipulations. They have also discovered that taking
the isolated cells through one cycle of rapid expansion (including
exposure to IL-2), rather than multiple cycles, yields lymphocyte
cultures with higher affinity and longer persistence in patients. Also,
they have found that administering nonmyeloablative lymphodepleting
chemotherapy prior to the reinfusion of lymphocytes creates a more
favorable environment within patients for the transferred cells to
execute target cell killing. These scientists envision that, for an ACT
immunotherapy to gain regulatory approval and successfully treat a wide
array of patients, it will need to be rapid, reliable, and technically
simple. One of the most critical factors to this approach is the
generation of effective lymphocyte cultures that will rapidly and
repeatedly attack the target cells when infused into patients.
Scientists at the NIH have developed a method of generating CD8+
selected ``young'' lymphocyte cultures for infusion into cancer
patients. Lymphocytes that spend fewer days in vitro between their
initial isolation from TIL and their ultimate reinfusion into patients
compared to lymphocytes cultured by previous ACT protocols are
considered young lymphocyte cultures. Young lymphocytes, typically 19-
35 days old when reinfused into patients, exhibit improved
proliferation, survival, and enhanced anti-tumor activity within
patients to yield greater tumor regression compared to older
[[Page 58294]]
lymphocytes, typically 44+ days old. Furthermore, the generation of
young lymphocyte cultures is more rapid, reliable, and technically
easier than previous ACT culturing methods. Young lymphocytes are
isolated from TIL, directed against a single isolated tumor cell
suspension, enriched for CD8 expression, and rapidly expanded once
using autologous feeder cells without testing the culture for antigen
specificity.
This approach to ACT offers a potentially significant improvement
and a valuable new immunotherapeutic tool for attacking tumors many
types of tumors. For diseases, such as metastatic melanoma, where
patients may only have weeks or months of life expectancy, this
technology, which provides for improved cell cultures prepared in less
time, can make a difference between life and death. 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.
Applications:
An improved immunotherapy methodology to treat and/or
prevent the recurrence of a variety of human cancers, such as melanomas
and glioblastomas, infectious diseases, and autoimmune diseases by
transferring young lymphocyte cultures engineered into cancer patients.
A technically simpler, more rapid, more clinically
reliable ACT procedure with greater potential to overcome the
technical, regulatory, and logistical hurdles of past ACT methods. This
technology could be broadly transferrable to a wide array of
institutions to treat a wide array of patients.
The immunotherapy component of a combination therapy
regimen aimed at targeting the specific tumor-associated antigens
expressed by the cancer cells of individual patients.
Advantages:
Technically simpler than previous ACT methods: Decreased
number of steps in the procedure and less analysis of the cell cultures
prior to reinfusion into patients.
More rapid than previous ACT methods: Adoptively
transferred lymphocytes spend fewer days undergoing in vitro culturing,
so they are introduced to patients with potentially short life
expectancies more quickly.
Reliable, life-saving technology: This technology is
anticipated by the inventors to yield greater tumor regression and more
objective clinical responses in patients compared to previous ACT
protocols and all previously attempted treatments for metastatic
melanoma.
Development Status: This technology is being utilized in a clinical
protocol for adoptive cell transfer. The technology is a critical
component of the successful immunotherapy regimen being used by the
inventors and other clinicians at the NCI. Patients enrolled in ACT
protocols are expected to show enhanced tumor regression and more
objective responses compared to results obtained with previous
protocols.
Market: Cancer continues to be a medical and financial burden on
U.S. public health. According to U.S. estimates, cancer is the second
leading cause of death with over 565,000 deaths reported in 2008 and
almost 1.5 million new cases were reported (excluding some skin
cancers) in 2008. In 2007, the NIH estimated that the overall cost of
cancer was $219.2 billion dollars and $89 billion went to direct
medical costs. Despite our increasing knowledge of oncology and cancer
treatment methods, the fight against cancer will continue to benefit
from the development of new therapeutics aimed at treating individual
patients.
Inventors: Mark E. Dudley and Steven A. Rosenberg (NCI).
Related Publications:
1. KQ Tran et al. Minimally cultured tumor-infiltrating lymphocytes
display optimal characteristics for adoptive cell therapy. J
Immunother. 2008 Oct;31(8):742-751.
2. SA Rosenberg and ME Dudley. Adoptive cell therapy for the
treatment of patients with metastatic melanoma. Curr Opin Immunol. 2009
Apr;21(2):233-240
Patent Status: HHS Reference No. E-273-2009/0--U.S. Provisional
Application No. 61/237,889 filed 28 Aug 2009
Related Technologies: HHS Reference No. E-275-2002/1--U.S. Patent
Application No. 10/526,697 filed 05 May 2005 (foreign counterparts in
Europe, Canada, and Australia)
Licensing Status: Available for licensing.
Licensing Contact: Samuel E. Bish, Ph.D.; 301-435-5282;
bishse@mail.nih.gov
Collaborative Research Opportunity: The Center for Cancer Research,
Surgery Branch, is seeking statements of capability or interest from
parties interested in collaborative research to further develop,
evaluate, or commercialize cell and gene therapy technologies, and
personalized medicines. Please contact John D. Hewes, Ph.D. at 301-435-
3121 or hewesj@mail.nih.gov for more information.
Treating Cancer With Anti-Angiogenic Chimeric Antigen Receptors
Description of Technology: Metastasis, the growth and spread of
cancer from a localized tumor to other sites in the body, is promoted
by the formation of new blood vessels through angiogenesis to ``feed''
the tumor. There is an urgent need to develop new therapeutic
strategies that combine fewer side-effects and more specific anti-tumor
activity in order to block cancer metastasis in patients. Adoptive
immunotherapy is a promising new approach to cancer treatment that
engineers an individual's innate and adaptive immune system to fight
against specific diseases, including the spread of cancer.
Chimeric antigen receptors (CARs) are hybrid proteins consisting of
the portion of an antibody that recognizes a tumor-associated antigen
(TAA) fused to protein domains that signal to activate the CAR-
expressing cell. Human cells that express CARs, most notably T cells,
can recognize specific tumor antigens in an MHC-unrestricted manner
with high reactivity. CARs are able to mediate an immune response that
promotes robust tumor killing in targeted cells.
Scientists at the National Institutes of Health (NIH) have
developed CARs with high affinity for the vascular endothelial growth
factor receptor 2 (VEGFR2) (also known as kinase domain region (KDR) in
humans and fetal liver kinase-1 (Flk-1) in mice) to utilize as an
antiangiogenic tumor therapy. VEGFR2 is expressed on non-cancerous
vascular endothelia cells, but is overexpressed on tumor endothelial
cells in a variety of cancers, especially solid tumors. VEGFR2
overexpression promotes tumor vasculature, growth, and metastasis. The
VEGFR2-specific CARs feature the antigen binding domain of the KDR-1121
or DC101 antibody, which recognize portions of the human and mouse
VEGFR2, respectively. This antibody component is fused to the
transmembrane and intracellular signaling domains of a T cell receptor
(TCR). These CARs combine high affinity recognition of VEGFR2 provided
by the antibody portion with the target cell killing activity of a cell
expressing an activated TCR. Infusion of these VEGFR2-specific CARs
into patients could prove to be a powerful new immunotherapeutic tool
for blocking angiogenic cancer metastasis by killing VEGFR2+ tumor
cells.
Applications:
Immunotherapeutics to treat and/or prevent the
reoccurrence of a variety of
[[Page 58295]]
human cancers that overexpress human VEGFR2 by introducing anti-VEGFR2
CAR expressing T cells into patients with metastatic cancer.
A possible prophylactic therapy to prevent the spread of
cancer in patients whose cancer is predicted to metastasize.
A drug component of a combination immunotherapy regimen
aimed at targeting the specific tumor-associated antigens expressed by
cancer cells within individual patients.
Advantages:
This discovery is widely applicable to many different
cancers: VEGFR2 is overexpressed in many metastatic cancers that
utilize angiogenesis to spread from their initial site of development.
An immunotherapy protocol using anti-VEGFR2 CAR could treat a variety
of cancer types.
Antiangiogenic tumor therapy is anticipated to generate
fewer side-effects compared to other treatment approaches: These CARs
can be delivered directly to the bloodstream to gain easy access to the
targeted tumor vascular endothelial cells with minimal effects to
normal tissues. Furthermore, destroying tumor blood vessels could
accelerate tumor cell death so that the therapy can be administered for
a shorter period of time. A reduced therapeutic timeframe and minimal
access to normal tissues should contribute to reduced side-effects and
lowered toxicity for this treatment.
The technology is anticipated to be highly effective and
killing metastatic cells: Most angiogenic tumor epithelial cells are
believed to overexpress VEGFR2 to a similar degree. Administering a
therapeutically effective amount of anti-VEGFR2 CARs to patients may
leave no or little tumor cells remaining with an opportunity to
metastasize. Many current angiogenesis therapies do not kill tumors,
but rather stabilize the tumor, so they require long periods of
administration.
Development Status: This technology could soon be ready for
clinical development since the inventors plan to initiate clinical
trials using CAR engineered lymphocytes for adoptive immunotherapy of
cancer.
Market: The Food and Drug Administration (FDA) has approved eight
therapies with antiangiogenic properties, including Avastin[reg],
Erbitux[reg], Vectibix[reg], Herceptin[reg], Tarceva[reg],
Nexavar[reg], Sutent[reg], Torisel\TM\, Velcade[reg], and
Thalomid[reg]. The majority of these drugs produced worldwide sales
exceeding an estimated $500 million in 2007. The fight against cancer
and its spread will continue to benefit from the development of new
therapeutics aimed at treating individual patients.
Cancer continues to be a medical and financial burden on U.S.
public health. Statistically, in the U.S. cancer is the second leading
cause of death with over 565,000 deaths reported in 2008 and almost 1.5
million new cases were reported (excluding some skin cancers) in 2008,
many with the potential to metastasize. In 2007, the NIH estimated that
the overall cost of cancer was $219.2 billion dollars and $89 billion
went to direct medical costs.
Inventors: Steven A. Rosenberg et al. (NCI).
Patent Status: HHS Reference No. E-205-2009/0--U.S. Provisional
Application No. 61/247,625 filed 01 Oct 2009.
Related Technologies:
E-045-2009/0--U.S. Provisional Application No. 61/154,080
filed 20 Feb 2009
E-312-2007/1--PCT Application No. PCT/US2008/077333 filed
23 Sep 2008
E-059-2007/2--PCT Application No. PCT/US2008/050841 filed
11 Jan 2008, which published as WO 2008/089053 on 24 Jul 2008
E-304-2006/0--U.S. Provisional Patent Application No. 60/
847,447 filed 26 Sep 2006; PCT Application No. PCT/US2007/079487 filed
26 Sep 2007, which published as WO 2008/039818 on 03 Apr 2008
E-093-1995/0--PCT Application No. PCT/US1996/04143 filed
27 Mar 1996, which published as WO 1996/30516 on 03 Oct 1996
E-093-1995/2--U.S. Non-Provisional Application No. 08/
084,994 filed 02 Jul 1993
Licensing Status: Available for licensing.
Licensing Contact: Samuel E. Bish, Ph.D.; 301-435-5282;
bishse@mail.nih.gov.
Collaborative Research Opportunity: The Center for Cancer Research,
Surgery Branch, is seeking statements of capability or interest from
parties interested in collaborative research to further develop,
evaluate, or commercialize this technology. Please contact John D.
Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more
information.
Dated: November 3, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. E9-27199 Filed 11-10-09; 8:45 am]
BILLING CODE 4140-01-P
