Preclinical Development of PEG-TNF

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 2R44CA085023-02
Agency Tracking Number: CA085023
Amount: $0.00
Phase: Phase I
Program: SBIR
Awards Year: 2004
Solicitation Year: N/A
Solicitation Topic Code: N/A
Solicitation Number: N/A
Small Business Information
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 (610) 524-7710
Business Contact
Phone: (859) 257-9027
Research Institution
DESCRIPTION (provided by applicant): Unformulated human tumor necrosis factor( (huTNF() has anti-tumor activity in mice, but there is little difference between the effective and lethal doses. Systemic administration of unformulated huTNFalpha has been tested in humans. All studies indicated the dose limiting toxicity was usually hypotension, the circulating half life was < 20 min and little anti-tumor activity was seen. Recent results from isolated limb perfusions with huTNFalpha for prolonged times indicated this cytokine to have marked anti-tumor activity in humans with melanoma. This suggests huTNFalpha may be therapeutically useful, provided the toxicity and short circulating half-life can be overcome. Formulation of other biologically active cytokines and proteins with polyethylene glycol (PEG) has significantly improved their safety and increases their circulating half-life. Examples include PEG-alpha interferon and PEG-GCSF, which are now approved by the FDA. The Phase 1 SBIR grant application proposed formulating huTNFalpha with PEG to increase its circulating half-life and increase its safety. An optimal formulation of huTNFalpha was found (termed huTNFalpha-SS PEG 20,000 mw). The circulating half-life, safety and efficacy of this formulation have been substantially increased compared with unformulated huTNFalpha in mice. In a Pre IND meeting with the FDA the final preclinical studies were identified and are the focus of this Phase 2 SBIR application. The specific aims are to: 1) produce cGMP huTNFalpha-SS PEG 20,000 mw; 2) finalize its pharmacological characterization; and 3) test the immunogenicity and its safety in animals according to GLP (Good Laboratory Practice). The data from these studies will provide the final information enabling the filing of an IND with the FDA to support human Phase I clinical testing.

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

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