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IMMUNOTHERAPY OF CLL WITH LENTIVIRAL EXPRESSED CD40-LIGAND

Award Number: R43CA124274
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: HEALTH SERVICES
PERIOD OF PERFORMANCE START DATE: 09/12/2006
PERIOD OF PERFORMANCE END DATE: 01/31/2007

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IMMUNOTHERAPY OF CLL WITH LENTIVIRAL EXPRESSED CD40-LIGAND - DESCRIPTION (provided by applicant): Despite recent advances, CLL as the most common leukemia remains largely incurable disease. The goal of the proposed project is to elucidate the ability of the lentiviral vector (LV) to provide efficient and clinically feasible delivery system for CD40-ligand (CD154), a very well known stimulator of T cells in chronic lymphocytic leukemia (CLL). This approach using LV-CD154 is expected to be superior to existing immune therapies using adenoviral vectors and will be basis for a future improved immune therapy for CLL and potentially other hematological malignancies. In Aim 1 we will develop SIN lentiviral vector that expresses CD40-ligand, as well as control vector expressing GFP. All vectors will contain the Drosophila melanogaster dNK-B10 gene using the E2A cleavage peptide sequence which will increase vector's safety. LV will be manufactured according to standard procedures and quality control tested prior to release for testing. In Aim 2 we will test the transduction efficiency of SIN.LV.CD154 and SIN.LV. GFP in vitro using primary CLL cells, and cell lines from different low grade lymphomas (CLL/SLL, MCL and FL) In addition, we will assess duration of expression of the transfected gene and test the relative potency of targeted cell stimulation with soluble CD154 versus cell bound CD154. During Phase I we propose to generate SIN-LV containing CD154 payload and to investigate its efficacy in CLL cells. Ultimately, during Phase II the SIN-LV-.CD154 will be tested in preclinical and clinical settings. During Phase III this therapy will be commercialized for CLL and possibly other hematological malignancies like mantle cell lymphoma and acute myeloid leukemia. The generated results will provide a basis for the development of a better and novel therapy for CLL and will significantly challenge the existing immune therapies using adenoviral vectors, mostly inadequate for providing stable and successful long term therapeutic activity.


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: 2006 ( Subtotal = $114,645 )
2006	2006	LENTIGEN CORPORATION	1450 SOUTH ROLLING ROAD	BALTIMORE	MD	21227	BALTIMORE	USA	Cancer Treatment Research	000	1	9/12/2006	NEW	$114,645
														Subtotal = $114,645

Grand Total All Awards = $114,645

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IMMUNOTHERAPY OF CLL WITH LENTIVIRAL EXPRESSED CD40-LIGAND

Award Number: R43CA124274

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: HEALTH SERVICES

PERIOD OF PERFORMANCE START DATE: 09/12/2006

PERIOD OF PERFORMANCE END DATE: 01/31/2007

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