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L-ASPARAGINASE IS AN IMPORTANT ADDITION TO COMBINATION CHEMOTHERAPY PROTOCOLS FOR CHILDHOOD ACUTE LYMPHOCYTIC LEUKEMIA.

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: N/A
Agency Tracking Number: 4797
Amount: $50,000.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: N/A
Solicitation Number: N/A
Timeline
Solicitation Year: N/A
Award Year: 1986
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
16020 Industrial Drive
Gaithersburg, MD 20877
United States
DUNS: N/A
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 DAVID M ANDERSON
 PRINCIPAL INVESTIGATOR
 (301) 258-0552
Business Contact
Phone: () -
Research Institution
N/A
Abstract

L-ASPARAGINASE IS AN IMPORTANT ADDITION TO COMBINATION CHEMOTHERAPY PROTOCOLS FOR CHILDHOOD ACUTE LYMPHOCYTIC LEUKEMIA. HOWEVER, IMMUNOLOGICAL REACTIONS TO THIS FOREIGN PROTEIN CAN GREATLY LIMIT ITS THERAPEUTIC EFFECTIVENESS. THEREFORE, THE PRODUCTION OF NON-CROSS REACTING L- ASPARAGINASE VARIANTS CAN EXPAND THE TIME AND BROADEN THE WAYS IN WHICH THE ENZYME CAN BE EFFECTIVELY GIVEN. L- ASPARAGINASE ISOLATED FROM ERWINIA CAROTOVORA DOES NOT CROSS-REACT WITH ANTIBODIES PRODUCED BY THE FDA-APPROVED ENZYME ISOLATED FROM ESCHERICHIA COLI AND HAS BEEN PROVEN TOBE CLINICALLY EFFECTIVE FOR PATIENTS WHO ARE ALLERGIC TO THEE. COLI ENZYME. THIS PROPOSAL WILL UTILIZE MODERN MOLECULARGENETIC AND PROTEIN ENGINEERING TECHNIQUES TO PRODUCE AN EXTREMELY COST-EFFECTIVE PRODUCTION STRAIN AND RECOVERY PROCESS FOR THIS IMPORTANT CLINICAL REAGENT. IN ADDITION, THESE TECHNIQUES MAY BE USED TO CREATE A FAMILY OF NON- CROSS-REACTING VARIANTS TO FURTHER EXPAND THE THERAPEUTIC EFFECTIVENESS OF L-ASPARAGINASE. IN PHASE I OF THE WORK, THE ERWINIA L-ASPARAGINASE GENE WILL BE CLONED. USING THIS CLONED GENE, PHASE II WILL INVOLVE (1) OVERPRODUCTION OF THEENZYME BY ALTERING THE TRANSCRIPTION, REGULATION, AND COPY NUMBER OF THE GENE; (2) DEVELOPMENT OF A PRODUCTION STRAIN FOR THE ENZYME BY PLACING THE GENE IS A NONPYROGENIC HOST THAT CAN BE GROWN TO HIGH CELL DENSITY AT LOW COST AND SECRETE THE PROTEIN; (3) IMPROVEMENT OF THE RECOVERY PROCESSFOR THE ENZYME BY ALTERING ITS AMINO ACID SEQUENCE WITH THE ADDITION OF RECEPTORS THAT WILL FACILITATE SEPARATION BY AFFINITY CHROMATOGRAPHY; AND (4) ALTERATION OF THE ANTIGEN CROSS-REACTIVITY OF THE PROTEIN BY MUTAGENESIS OF IMMUNODOMINANT REGIONS.

* Information listed above is at the time of submission. *

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