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THERAPEUTIC POTENTIAL OF TCR-LIKE RECOMBINANT ANTIBODIES

Award Number: R01CA115550
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2005
PERIOD OF PERFORMANCE END DATE: 12/31/2010

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THERAPEUTIC POTENTIAL OF TCR-LIKE RECOMBINANT ANTIBODIES - DESCRIPTION (provided by applicant): Long term objectives: Specificity in the cellular immune system is controlled and regulated by the T cell receptor (TCR), which specifically recognizes peptide/Major histocompatability complex (MHC) molecules. By using recombinant DNA and antibody engineering approaches, we developed a unique approach to rapidly identify and isolate unique antibodies, called T-Cell Receptor-Like antibodies (TCRLs), which recognize and bind to tumor-associated MHC-peptide complexes normally recognized by killer T-cells (CTLs). This affords us the opportunity to transform the unique specificity of tumor CTLs into high affinity soluble recombinant antibodies. TCRL antibodies offer important advantages over CTLs. TCRL antibodies combine the best features of both arms of the immune system: 1) the ability of antibodies to bind with high affinity as soluble molecules not susceptible to the regulatory influences that limit T cells, 2) and the ability of T cells to use the MHC internal surveillance mechanism to detect, from the outside of the cells, any foreign or abnormal protein within any cell in the body. The long term objectives of the proposed research are to evaluate the potential of melanoma-specific TCR-like antibodies to serve as a targeting moiety and/or effector molecule that may potentiate a better immune activity and potentially be developed as a new immunotherapeutic modality for melanoma. Specific Aims: The specific aims that we would like to achieve in this grant application include:1)To evaluate the targeting potential of melanoma specific Toxin-armed TCR-like antibodies recombinant fragments in vitro and in vivo 2)To evaluate the in vitro and in vivo biological activities of melanoma specific TCR-like antibodies as whole antibody molecules 3)To elucidate the molecules events and signal transduction pathways that lead to the biological activities of TCR-like antibodies on melanoma tumor cells. Research & Development Methods: We have developed a large panel of TCRL antibodies targeting various melanoma-specific T cell epitopes derived from several melanoma differentiation antigens. Using these characterized molecules we will explore their biological properties as recombinant antibody fragments and as whole antibodies and evaluate their therapeutic potential in vitro as well as in animal models.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2010 ( Subtotal = $0 )
2010	2008	TECHNION ISRAEL INSTITUTE TECHNOLOGY	SENATE BLDG, ROOM 157	TECHNTON CITY				ISR	Cancer Cause and Prevention Research	000	4	5/12/2010	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2008 ( Subtotal = $202,248 )
2008	2008	TECHNION ISRAEL INSTITUTE TECHNOLOGY	SENATE BLDG, ROOM 157	TECHNTON CITY				ISR	Cancer Cause and Prevention Research	000	4	6/20/2008	NON-COMPETING CONTINUATION	$202,248
														Subtotal = $202,248

Issue Date FY: 2007 ( Subtotal = $202,248 )
2007	2007	TECHNION ISRAEL INSTITUTE TECHNOLOGY	SENATE BLDG, ROOM 157	TECHNTON CITY				ISR	Cancer Cause and Prevention Research	000	3	6/29/2007	NON-COMPETING CONTINUATION	$202,248
														Subtotal = $202,248

Issue Date FY: 2006 ( Subtotal = $208,288 )
2006	2006	TECHNION ISRAEL INSTITUTE TECHNOLOGY	SENATE BLDG, ROOM 157	TECHNTON CITY				ISR	Cancer Cause and Prevention Research	000	2	5/16/2006	NON-COMPETING CONTINUATION	$208,288
														Subtotal = $208,288

Issue Date FY: 2005 ( Subtotal = $213,300 )
2005	2005	TECHNION ISRAEL INSTITUTE TECHNOLOGY	SENATE BLDG, ROOM 157	TECHNTON CITY				ISR	Cancer Cause and Prevention Research	000	1	8/22/2005	NEW	$213,300
														Subtotal = $213,300

Grand Total All Awards = $826,084

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THERAPEUTIC POTENTIAL OF TCR-LIKE RECOMBINANT ANTIBODIES

Award Number: R01CA115550

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2005

PERIOD OF PERFORMANCE END DATE: 12/31/2010

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