26704 Federal Register / Vol. 74, No. 105 / Wednesday, June 3, 2009 / Notices 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Centers for Disease Control and 

Prevention 

Draft Guideline for Prevention of 

Catheter-Associated Urinary Tract 

Infections 2008 

AGENCY: Centers for Disease Control and 

Prevention (CDC), Department of Health 

and Human Services (DHHS). 

ACTION: Notice of document availability 

and request for public comment. 

SUMMARY: This notice is a request for 

review of and comment on the Draft 

Guideline for Prevention of CatheterAssociated Urinary Tract Infections 

2008, available on the following Web 

site: http://wwwnd.cdc.gov/ 

publiccomments/. This document is for 

use by infection prevention staff, 

healthcare epidemiologists, healthcare 

administrators, nurses, other healthcare 

providers, and persons responsible for 

developing, implementing, and 

evaluating infection prevention and 

control programs for healthcare settings 

across the continuum of care. The 

guideline updates and expands the 1981 

Guideline for Prevention of Catheterassociated Urinary Tract Infections. 

DATES: Comments must be received on 

or before July 6, 2009. 

ADDRESSES: Comments on the Draft 

Guideline for Prevention of CatheterAssociated Urinary Tract Infections 

should be submitted by e-mail to 

cauti@cdc.gov or by mail to CDC, 

Division of Healthcare Quality 

Promotion, Attn: Resource Center, 1600 

Clifton Rd., NE., Mailstop A–31, 

Atlanta, Georgia 30333; or by fax 404– 

639–4049. 

SUPPLEMENTARY INFORMATION: The Draft 

Guideline for Prevention of CatheterAssociated Urinary Tract Infections 

addresses prevention of CAUTI for 

patients in need of either short- or longterm urinary catheterization in any type 

of healthcare setting and includes data 

for indwelling urethral catheterization 

as well as alternative methods of urinary 

drainage. The guideline also includes 

specific recommendations for 

implementation, performance 

measurement, and surveillance. 

Recommendations for further research 

are also included to address the 

knowledge gaps in CAUTI prevention 

identified during the literature review. 

The guideline is based on a targeted 

systematic review of the best available 

evidence with explicit links between the 

evidence and recommendations. 

Dated: May 21, 2009. 

James D. Seligman, 

Chief Information Officer, Centers for Disease 

Control and Prevention. 

[FR Doc. E9–12901 Filed 6–2–09; 8:45 am] 

BILLING CODE 4163–18–P 

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. 

Novel Method of Treating Cancer Using 

Ixolaris 

Description of Technology: Aggressive 

tumors spread between tissues in a 

process known as metastasis. Tumor 

metastasis, particularly with regard to 

brain cancer (gliomas), has been linked 

to the aberrant expression of membranebound tissue factor (TF). TF normally 

functions as a blood coagulation factor 

and can lead to the production of proangiogenesis factors such as vascular 

endothelial growth factor (VEGF). By 

doing this in the vicinity of tumors, TF 

may enhance both tumor growth and the 

ability of tumors to metastasize. 

Ixolaris is a protein that prevents the 

initiation of blood coagulation, 

specifically by inhibiting TF. NIH 

inventors have explored the possibility 

that Ixolaris could be effective as an 

anti-cancer therapy. As an inhibitor of 

TF, Ixolaris could potentially inhibit the 

function of TF, thereby reducing the 

ability of a tumor to develop and to 

metastasize. Recent data show that 

Ixolaris has the ability to prevent tumor 

growth in vivo using mouse xenograft 

models. Importantly, the inhibition in 

vivo occurred without noticeable 

bleeding. Since Ixolaris is not 

immunogenic, it might be an excellent 

candidate as an anti-cancer therapeutic. 

Application: Treatment and 

prevention of tumor growth and 

metastasis by inhibiting TF and blood 

vessel formation. 

Advantages: Provides a novel 

mechanism for preventing tumor 

metastasis. 

Development Status: Preclinical stage 

of development. 

Inventors: Ivo Francischetti (NIAID) et 

al. 

Patent Status: U.S. Provisional 

Application No. 61/161,223 (HHS 

Reference No. E–148–2009/0–US–01). 

For more information, see: 

1. U.S. Patent 7,078,508 entitled 

‘‘Ixodes Scapularis Tissue Factor 

Pathway Inhibitor’’. 

2. IM Francischetti et al. Ixolaris, a 

novel recombinant tissue factor pathway 

inhibitor (TFPI) from the salivary gland 

of the tick, Ixodes scapularis: 

identification of factor X and factor Xa 

as scaffolds for the inhibition of factor 

VIIa/tissue factor complex. Blood 2002 

May 15;99(10):3602–3612. 

3. RA Nazareth et al. Antithrombotic 

properties of Ixolaris, a potent inhibitor 

of the extrinsic pathway of the 

coagulation cascade. Thromb Haemost. 

2006 Jul;96(1):7–13. 

Licensing Status: Available for 

licensing. 

Licensing Contact: David A. 

Lambertson, PhD; 301–435–4632; 

lambertsond@mail.nih.gov. 

Collaborative Research Opportunity: 

The NIAID, OTD, is seeking statements 

of capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize Ixolaris for cancer 

treatment. Please contact Dana Hsu at 

301–496–2644 for more information. 

Immortalized Virus-Free Human 

Placental Cell Lines 

Description of Technology: This 

technology provides immortalized 

virus-free human placental cell lines. To 

develop these cell lines, human 

placental cells were immortalized with 

adenovirus-origin-minus (ori-)-simian 

virus-40 (SV40) recombinant viruses 

containing either wild-type or 

temperature-sensitive (ts) A mutants of 

SV40. Cells transformed with the SV40 

tsA chimera (HP–A1 and HP–A2), but 

not the SV40 wild-type chimera (HP– 

W1), were conditional for 


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Federal Register / Vol. 74, No. 105 / Wednesday, June 3, 2009 / Notices 26705 

transformation. All three cell lines 

expressed trophoblast-specific genes, 

including placental specific genes and 

the alpha- and beta-subunits of hCG. 

These immortalized virus-free human 

placental cell lines expressing major 

proteins of human trophoblasts provide 

efficient in vitro models to study 

placental functions. 

Inventor: Janice Y. Chou (NICHD). 

Publication: KJ Lei, Y Gluzman, CJ 

Pan, JY Chou. Immortalization of virusfree human placental cells that express 

tissue-specific functions. Mol 

Endocrinol. 1992 May; 6(5):703–712. 

Patent Status: HHS Reference No. E– 

052–2009/0—Research Tool. Patent 

protection is not being pursued for this 

technology. 

Licensing Status: Available for 

licensing under a Biological Materials 

License Agreement. 

Licensing Contact: Suryanarayana 

(Sury) Vepa, PhD, J.D.; 301–435–5020; 

vepas@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Institute of Child Health 

and Human Development, Section on 

Cellular Differentiation, is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize Immortalized Virus-Free 

Human Placental Cell Lines. Please 

contact Joseph Conrad III, PhD at 301– 

435–3107 or jmconrad@mail.nih.gov for 

more information. 

Broadly Applicable Modules for 

Improved Expression and Detection of 

Membrane Proteins 

Description of Technology: NIH 

investigators have designed and tested a 

set of expression modules that are 

applicable to a wide variety of 

membrane proteins. Prior to this 

invention, cloned membrane proteins 

have sometimes been difficult to detect 

due to the lack of effective antibodies. 

Moreover, currently available 

expression vectors lack the signal 

sequences, tags, and multiple cloning 

sites to clone membrane proteins and 

express them on the cell surface. This 

invention is the first of its kind to 

contain all of these elements to facilitate 

biochemical studies on membrane 

proteins. 

This technology is a set of nucleic 

acid modules designed for the 

expression and tagging of membrane 

proteins in mammalian cells. The 

module includes a signal peptide, an 

exchangeable tag, and a multiple 

cloning site. The gene of a membrane 

protein may be conveniently inserted 

into the multiple cloning site, and the 

signal peptide will target the cloned 

membrane protein to the cell surface. 

The tag, in frame with the signal 

peptide, is either a fluorescent protein 

or an epitope for a known antibody, 

both of which enable detection of the 

protein by several standard biochemical 

methodologies. 

Applications: This technology can 

provide improved expression and 

detection of membrane proteins in 

common laboratory cell lines. 

Development Status: Each module 

contains either one of two different 

epitope tag, and the expression vector 

contains either zeocin- or neomycinresistant markers. There are two sets of 

module (four vectors) available. 

Inventors: Li Lin et al. (NIA). 

Publication: J Pang, X Zeng, R–P Xiao, 

EG Lakatta, L Lin. Design, generation, 

and testing of mammalian expression 

modules that tag membrane proteins. 

Protein Science, in press (2009). 

Patent Status: U.S. Provisional 

Application No. 61/142,531 filed 05 Jan 

2009 (HHS Reference No. E–016–2009/ 

0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Fatima Sayyid, 

MHPM; 301–435–4521; 

Fatima.Sayyid@nih.hhs.gov. 

Collaborative Research Opportunity: 

The National Institute on Aging, 

Laboratory of Cardiovascular Sciences, 

is seeking statements of capability or 

interest from parties interested in 

collaborative research to further 

develop, evaluate, or commercialize the 

technology of mammalian membrane 

protein expression and detection. Please 

contact Vio Conley at 301–496–0477 or 

conleyv@mail.nih.gov for more 

information. 

Inhibitors of CD25 To Treat 

Autoimmune Diseases and Tumors 

Description of Technology: This 

invention discloses therapeutics for the 

treatment of Multiple Sclerosis, uveitis, 

and certain cancers by providing 

methods and compositions for 

selectively blocking CD25 on T cells or 

dendritic cells. The therapeutics 

developed using the current 

technologies have the potential to 

exhibit superior specificity and minimal 

side-effects. In this invention, NIH 

investigators, for the first time, 

demonstrate that mature dendritic cells 

(mDC) use CD25 for trans-presentation 

of IL–2, and the blockade of CD25 on 

the surface of mDCs abrogates T cell 

proliferation. Further, CD25 expression 

on T cells is not only dispensable for 

their proliferation, but it also limits 

effector T cell survival. These 

observations form the basis for the 

development of novel therapies for 

certain cancers and autoimmune 

disorders. 

Applications: Therapeutics for 

autoimmune diseases; Therapeutics for 

tumors. 

Development Status: Early stage. 

Inventors: Bibiana Bielekova et al. 

(NINDS). 

Publication: Manuscript submitted for 

publication. 

Patent Status: U.S. Provisional 

Application No. 61/201,589 filed 12 Dec 

2008 (HHS Reference No. E–007–2009/ 

0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Suryanarayana 

(Sury) Vepa, PhD, J.D.; 301–435–5020; 

vepas@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Institute of Neurological 

Disorders and Stoke is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize methods of treating 

multiple sclerosis by administering 

agents that block the interaction of 

dendritic cells and T cells via CD25. 

Please contact Dr. Martha Lubet at 301– 

435–3120, e-mail: lubetm@mail.nih.gov 

for more information. 

Methods for Identifying Breast Cancer 

Patients for Therapy With mTOR 

Inhibitors 

Description of Technology: This 

technology relates to methods of 

identifying individuals with invasive 

breast cancer who may benefit from 

treatment with an inhibitor of 

mammalian Target of Rapamycin 

(mTOR), particularly those having a 

gene amplification including 

chromosome 8p11–12 or a portion 

thereof. Chromosome 8p11–12 is the 

second most commonly amplified 

region in breast cancer cases, after HER2 

amplification at chromosome 17. 

Similar to HER2 amplification, the 

amplification of 8p11–12 is associated 

with decreased survival. However, 

whereas patients diagnosed with HER2 

amplifications can be more effectively 

treated with adjuvant therapy using 

HER2 inhibitors such as trastuzumab, 

no specific therapy has been identified 

for breast cancer patients having an 

amplification of chromosome 8p11–12. 

Investigators at NIH have shown that 

amplification of chromosome 8p11–12 

leads to increased copy number of the 

gene for eukaryotic translation initiation 

factor 4E binding protein 1, or EIF4EBP1 

and elevated expression of the protein 

in these breast cancer cell lines. EIF4E 

is a rate limiting component of a multisubunit complex that recruits 40S 

ribosomal subunits to the 5′ end of 


PWALKER on PROD1PC71 with NOTICES
26706 Federal Register / Vol. 74, No. 105 / Wednesday, June 3, 2009 / Notices 

mRNAs. EIF4EBP1 interacts and 

inhibits EIF4E complex assembly and 

thus, represses translation. In breast 

cancer cell lines with EIF4EBP1 

amplification, the elevated EIF4EBP1 is 

largely inactivated via 

hyperphosphorylation. As the 

phosphorylation of EIF4EBP1 is 

controlled by mTOR, its 

hyperphosphorylation can be reversed 

with rapamycin. Indeed, rapamycin is 

much more effective in inhibiting the 

formation of active translational 

complex and the growth of breast cancer 

cells with chromosome 8p11–12/ 

EIF4EBP1 amplification. Thus, 

detection of chromosome 8p11–12 

amplification, and/or over-expression or 

increased phosphorylation of EIF4EBP1 

can be used to identify breast cancer 

patients for treatment with inhibitors of 

mTOR, such as rapamycin or its 

derivatives or analogs. 

Applications 

• Diagnostic kit for measuring DNA 

amplification of chromosome 8p11–12 

and/or EIF4EBP1 to identify breast 

cancer patients that could benefit from 

mTOR inhibitor drugs. 

• Diagnostic kit for measuring 

EIF4EBP1 mRNA or protein levels to 

help identify breast cancer patients that 

could benefit from mTOR inhibitor 

drugs. 

Advantages 

• This molecular diagnostics may 

optimize the therapeutic use of mTOR 

inhibitors in the treatment of breast 

cancer. 

• This molecular diagnostics may 

stratify breast cancer patients for 

clinical trials with mTOR targeted 

agents for increased responses. 

Development Status: Early stage; Preclinical data available. 

Market: Breast cancer is the most 

common cancer among women in the 

United States, other than skin cancer. It 

is the second leading cause of cancer 

death in women, after lung cancer. An 

estimated 182,460 new cases of invasive 

breast cancer were expected to occur 

among women in the U.S. during 2008. 

Amplification of chromosome 8p11–12 

occurs in about 10–15% of the invasive 

breast cancer cases. 

Inventors: Liang Cao and Paul S. 

Meltzer (NCI). 

Publications: None related to this 

technology. 

Patent Status: U.S. Provisional 

Application No. 61/152,920 filed 16 Feb 

2009 (HHS Reference No. E–340–2008/ 

0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Surekha Vathyam, 

PhD; 301–435–4076; 

vathyams@mail.nih.gov. 

Collaborative Research Opportunity: 

The Genetics Branch at National Cancer 

Institute is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize. Please contact John D. 

Hewes, PhD at 301–435–3121 or 

hewesj@mail.nih.gov for more 

information. 

Method for the Diagnosis and Prognosis 

of Age-Related Cardiovascular 

Disorders 

Description of Technology: NIH 

investigators have discovered a method 

for the diagnosis and prognosis of 

cardiovascular aging. Current 

methodologies include the measurement 

of patient lipid profiles or expression of 

up to two proteins. In contrast, this 

technology utilizes the expression levels 

of a panel of proteins not previously 

known to be related to cardiovascular 

aging and may prove to be a more 

accurate diagnostic or prognostic of 

cardiovascular aging than currently 

available tests or it may improve the 

accuracy of currently available tests 

when used in concert. 

The technology relates to methods for 

determining susceptibility to having an 

extremely common age-associated 

vascular disorder. It also describes the 

subsequent use of these proteins as 

markers for disease. While the 

underlying cellular and molecular 

mechanisms of age-related vascular 

disease remain largely undefined, the 

expression levels of the genes described 

in this technology have been 

empirically determined to differ 

between healthy and age-inflamed 

arterial tissue. Further, this technology 

includes a companion mass 

spectroscopic-based methodology for 

reproducible quantification of specific 

expression levels of interest. 

Application: Diagnosis of age-related 

vascular disorder. 

Development Status: Early stage. 

Inventors: Mingyi Wang et al. (NIA). 

Patent Status: U.S. Provisional 

Application No. 61/154,329 filed 20 Feb 

2009 (HHS Reference No. E–219–2008/ 

0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Fatima Sayyid, 

MHPM; 301–435–4521; 

Fatima.Sayyid@nih.hhs.gov. 

Collaborative Research Opportunity: 

The National Institute on Aging, 

Cardiovascular Biology Unit-Vascular 

Group, is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize idea of how to assess and 

retard accelerated arterial aging and its 

attendant risks for atherosclerosis and 

hypertension. Please contact Vio Conley 

at 301–496–0477 or 

conleyv@mail.nih.gov for more 

information. 

CCR5-Specific Human Monoclonal 

Antibodies 

Description of Technology: The 

subject invention describes the antiCCR5 monoclonal antibodies, their 

fusion protein, conjugates, derivatives, 

or fragments, DNA sequences encoding 

such antibodies, host cells containing 

such DNA sequences, as well as the 

methods to produce them 

recombinantly and their 

pharmacological composition. 

It has been demonstrated that the HIV 

co-receptor CCR5 plays an important 

role in virus entry. The subject 

antibodies exhibited neutralization 

activity against HIV–1 infection by 

binding to cell associated CCR5 in vitro. 

Therefore, subject anti-CCR5 antibodies 

can be useful research materials for the 

research in HIV/AIDS fields. 

Applications: Research tools. 

Development Status: In vitro data is 

available at this time. 

Inventors: Dimiter S. Dimitrov and 

Mei-Yun Zhang (NCI). 

Related Publications 

1. C Pastori et al. Long-lasting CCR5 

internalization by antibodies in a subset 

of long-term nonprogressors: a possible 

protective effect against disease 

progression. Blood. 2006 Jun 

15;107(12):4825–4833. 

2. MY Zhang, B Vu, CC Huang, I 

Sidirov, V Choudhly, PD Kwong, DS 

Dimitrov. Identification of human 

monoclonal antibodies specific for 

CCR5 from an antibody library derived 

from HIV-infected long-term nonprogressors. Retrovirology. 2006 Dec 

21;3 Suppl 1:S61. 

3. DS Dimitrov. Virus entry: 

molecular mechanisms and biomedical 

applications. Nat Rev Microbiol. 2004 

Feb;2(2):109–122. 

Patent Status: HHS Reference No. E– 

297–2006/0—Research Tool. Patent 

protection is not being pursued for this 

technology. 

Licensing Status: Available for 

licensing. 

Licensing Contact: Sally Hu, PhD; 

301–435–5606; HuS@mail.nih.gov. 


PWALKER on PROD1PC71 with NOTICES
Federal Register / Vol. 74, No. 105 / Wednesday, June 3, 2009 / Notices 26707 

Dated: May 27, 2009. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E9–12873 Filed 6–2–09; 8:45 am] 

BILLING CODE 4140–01–P 

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 Markers for Melanoma 

Description of Technology: This 

invention relates to diagnostic and 

prognostic markers for melanoma. It 

discloses the identification of somatic 

mutations in genes of the 

microphthalmia-associated transcription 

factor (MITF) pathway in patients with 

melanoma. 

Melanoma is an aggressive and often 

fatal cancer with increasing incidence 

worldwide. Previous studies have 

linked the MITF pathway to the 

progression of melanoma. However, 

little is known about somatic mutations 

in genes of the MITF pathway that 

contribute to the development and 

progression of melanoma. To assess the 

role of the MITF pathway in melanoma, 

NIH investigators evaluated primary and 

metastatic melanoma samples for the 

presence of somatic mutations in two 

genes of the MITF pathway, MITF and 

SRY (sex determining region Y)—box 10 

(SOX10). They identified 16 previously 

unidentified somatic mutations in these 

genes. These studies suggest that MITF 

and SOX10 genes be used as diagnostic 

markers in human metastatic melanoma. 

Applications 

• Diagnosis and prognosis of patients 

with melanoma by detecting any 

mutations in the MITF or SOX10 gene. 

• Selection of therapy for melanoma 

patient; an MITF inhibitor can be 

selected for therapy if the patient has 

any of the disclosed mutations in MITF. 

Market: Cancer is the second leading 

cause of death in the U.S. There is an 

acute need for cancer biomarkers that 

can be detected from clinically relevant 

samples and used for early diagnosis, 

therapeutic follow-up and prognosis of 

malignant diseases. Melanoma is the 

most serious type of cancer of the skin. 

The percentage of people who develop 

melanoma has more than doubled in the 

past 30 years. There are 68,720 

estimated new cases and 8,650 

estimated deaths from melanoma in the 

United States in 2009, according to the 

National Cancer Institute. 

Inventors: Yardena R. Samuels et al. 

(NHGRI). 

Publication: Cronin JC WJ, Loftus SK, 

Prickett TD, Wei X, Ridd, Vemula S, 

Burrell AS, Agrawal NS, Lin JC, Banister 

CE, Buckhaults P, Rosenberg SA, 

Bastian BC, Pavan WJ, Samuels Y: 

Frequent mutations in the MITF 

pathway in melanoma. Pigment Cell and 

Melanoma Research 2009, (In Press). 

Patent Status: U.S. Provisional 

Application No. 61/214,415 filed 22 Apr 

2009 (HHS Reference No. E–053–2009/ 

0–US–01). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Betty B. Tong, 

Ph.D; 301–594–6565; 

tongb@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Human Genome Research 

Institute’s Cancer Genetics Branch is 

seeking statements of capability or 

interest from parties interested in 

collaborative research to further 

develop, evaluate, or commercialize 

these newly identified candidate 

melanoma diagnostic and prognostic 

markers. Please contact NHGRI’s 

Technology Development Coordinator 

(TDC) Claire T. Driscoll at 

cdriscol@mail.nih.gov for more 

information. 

T Cells Attacking Cancer: T Cell 

Receptors That Recognize the 

Tyrosinase Tumor Antigen 

Description of Technology: A problem 

with current chemotherapy-based 

cancer treatments is the harsh sideeffects associated with many cancer 

drugs. Thus, there is an urgent need to 

develop new therapeutic strategies 

combining fewer side-effects and more 

specific anti-tumor activity. Adoptive 

cell transfer (ACT) is a promising new 

immunotherapeutic approach to treat 

cancer and other diseases by directing 

an individual’s innate and adaptive 

immune system to recognize specific 

disease-associated antigens. 

T cell receptors (TCRs) are proteins 

that recognize antigens in the context of 

infected or transformed cells and 

activate T cells to mediate an immune 

response and destroy abnormal cells. 

TCRs consist of two domains, one 

variable domain that recognizes the 

antigen and one constant region that 

helps the TCR anchor to the membrane 

and transmit recognition signals by 

interacting with other proteins. 

Scientists at the National Institutes of 

Health (NIH) have isolated T cells that 

recognize the human tyrosinase tumorassociated antigen (TAA) from the 

tumor infiltrating lymphocytes (TIL) of 

a melanoma cancer patient. The human 

tyrosinase antigen is a tumor antigen 

expressed in a variety of cancers, 

including skin cancer (melanoma) and 

brain cancer (glioblastoma). Utilizing 

the tyrosinase specific T cells, these 

scientists developed human/mouse 

hybrid TCRs with enhanced affinity for 

the tyrosinase TAA. The TCR sequences 

were modified by making specific 

amino acid substitutions and replacing 

certain TCR regions with mouse 

homologues. These TCRs also showed 

CD8-independency and, thus, can be 

expressed in both CD8 and CD4 T cells. 

T cells expressing these engineered 

TCRs recognize skin and brain tumor 

cells in culture. These T cells also 

exhibit enhanced cytokine induction 

and better tumor reactivity compared to 

unmodified TCRs. Previous versions of 

gene-modified T cells developed by NIH 

researchers demonstrated objective 

clinical responses in some cancer 

patients, which have validated genemodified T cell immunotherapy as a 

promising cancer treatment strategy. 

TCRs directed against the tyrosinase 

TAA could serve as valuable new 

immunotherapeutic tools for attacking 

tumors, especially in patients whose 

tumors do not express other common 

TAAs. 

Applications 

• Immunotherapeutics to treat and/or 

prevent the recurrence of a variety of 

human cancers, including melanomas 

and glioblastomas, that express 

tyrosinase by transferring T cells 

engineered with tyrosinase-specific 

TCRs into cancer patients. 


PWALKER on PROD1PC71 with NOTICES