DEVELOPMENT OF IMMUNOTOXINS USING A MUTANT OF EXOTOXIN A

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: N/A
Agency Tracking Number: 16286
Amount: $384,819.00
Phase: Phase II
Program: SBIR
Awards Year: 1993
Solicitation Year: N/A
Solicitation Topic Code: N/A
Solicitation Number: N/A
Small Business Information
Inland Laboratorytories
2600 Stemmons Freeway, Dallas, TX, 75207
DUNS: N/A
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 Fulton, Robert J
 Principal Investigator
 (214) 637-5804
Business Contact
 1 R43 AI30839-01
Phone: () -
Research Institution
N/A
Abstract
THE GOAL OF THE RESEARCH IS TO DETERMINE WHETHER A NEW MUTANT OF PSEUDOMONAS AERUGINOSA ETA WITH IMPAIRED CELL SURFACE RECEPTOR BINDING ACTIVITY WILL ALLOW THE CONSTRUCTION OF IMMUNOTOXINS WITH SUPERIOR CYTOTOXICITY TO IMMUNOTOXINS CONSTRUCTED WITH RICIN A CHAIN. THE LONG TERM OBJECTIVE OF THIS RESEARCH IS TO IMPROVE THE CYTOTOXIC POTENCY OF IMMUNOTOXINS BY USING A MORE POTENT TOXIN THAN IS CURRENTLY AVAILABLE. THE SPECIFIC AIMS ARE TO DETERMINE OPTIMAL CONDITIONS AND CROSSLINKING REAGENTS FOR THE MODIFICATION AND CONJUGATION OF THE MUTANT EXOTOXIN TO ANTIBODY, AND TO COMPARE DIRECTLY THE SPECIFIC AND NON-SPECIFIC CYTOTOXICITY OF THESE CONJUGATES TO CONJUGATES PREPARED WITH RICIN A CHAIN. IMMUNOTOXINS PREPARED EITHER BY DISULFIDE OR THIOETHER LINKAGE BETWEEN ANTIBODY AND THE MUTANT EXOTOXIN WILL BE PREPARED AND TESTED FOR CYTOTOXICITY TO ESTABLISH OPTIMAL CONJUGATION PARAMETERS. BASED ON THESE FINDINGS, IMMUNOTOXINS WILL BE PREPARED WITH THE MUTANT ETA AND SEVERAL MABS. THE SPECIFIC AND NON-SPECIFIC TOXICITY OF THESE IMMUNOTOXINS AND RICIN A CHAIN IMMUNOTOXINS PREPARED WITH THE SAME ANTIBODIES WILL BE DIRECTLY COMPARED BY TESTING ON IN VITRO TARGET CELL LINES. THE SUCCESSFUL ATTAINMENT OF THE OBJECTIVES OF THIS RESEARCH WILL EVENTUALLY MAKE IMMUNOTOXINS WITH INCREASED CYTOTOXIC POTENCY COMMERCIALLY AVAILABLE BOTH FOR RESEARCH PURPOSES AND FOR THE THERAPY OF HUMAN DISEASE.

* information listed above is at the time of submission.

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