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Targeted Prodrug Therapy of Liver Cancers

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
70587
Program Year/Program:
2004 / SBIR
Agency Tracking Number:
CA105617
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
ACCLAIM BIOTECHNOLOGY
ACCLAIM BIOTECHNOLOGY 3520 PLUMB ST HOUSTON, TX 77005 0292
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Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2004
Title: Targeted Prodrug Therapy of Liver Cancers
Agency: HHS
Contract: 1R43CA105617-01
Award Amount: $100,000.00
 

Abstract:

DESCRIPTION (provided by applicant): Hepatocellular carcinoma (HCC) and colorectal cancer (CRC) are among the most common and deadly malignancy worldwide. CRC is the second leading cause of cancer-related death in the USA, mostly due to metastases to the liver. 5-fluorouracil (5-FU) remains the mainstay of combination chemotherapy for liver cancers including non-resectable liver metastases. Recent studies demonstrated that regional 5-FU-based chemotherapy by directly hepatic infusion showed improved response rates and survival for CRC patients as compared with those with systemic treatment. However, this delivery system is technically complicated, highly invasive, risky and costly. The present application is a patented delivery system for improved chemotherapy of liver cancer and metastasis. It utilizes a recombinant fusion protein consisted of the malarial circumsporozoite (CS) protein, a hepatocyte-specific targeting ligand, linked to the bacterial cytosine deaminase (CD), a suicidal gene product which catalyzes the production of 5-FU from its prodrug 5- fluorocytosine (5-FC). We have demonstrated that the CD-CS fusion protein can be internalized in a cell type-specific manner. More importantly, the internalized protein is stable for at least four weeks and exerts bystander cell-killing effects upon the administration of the prodrug 5-FC. The prolonged stability can be attributed to the fact that the internalized fusion protein is entrapped in the particular compartment(s) that are free from the cytoplasmic degradation machinery. To further develop and commercialize this system, we propose the following 2 specific aims: (1) to construct deletion mutants and modified versions of CD-CS for increasing yield, stability and activity of the fusion protein; and (2) to optimize the production of the modified CD-CS protein and to determine their effectiveness in scale-up preparations for product manufacturing and future clinical trials. This novel prodrug targeting therapy is effective, technically simple, non-invasive and cost effective, which should have enormous commercial potential.

Principal Investigator:

John Y. Chan
7137923214
CHANYHJOHN@HOTMAIL.COM

Business Contact:


7137923256
Small Business Information at Submission:

ACCLAIM BIOTECHNOLOGY
ACCLAIM BIOTECHNOLOGY 3520 PLUMB ST HOUSTON, TX 77005

EIN/Tax ID: 470913969
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No