Fiscal Year:
2001
Title:
MODIFIED TNF-ALPHA: AN ANTI CANCER THERAPY
Agency:
HHS
Contract:
N/A
Award Amount:
$99,962.00
Abstract:
DESCRIPTION (PROVIDED BY APPLICANT): The long-term goal of the proposed
research is the development of effective anti-cancer agents, modified human
tumor necrosis factor-alphas (hTNFas). TNFa is a potent anti-neoplastic agent
but its therapeutic application has been limited by its significant side
effects. However, TNFa can be modified so that it retains its anti-tumor
activities while its deleterious effects are reduced. This has been
accomplished by mutation of TNFa and derivitization of TNFa with polyethylene
glycol (PEG). This proposal focuses on the characterization and comparison of
mutant and wild hTNFas modified with 20 kDa PEGs.
The specific aims are to:
1) pharmacologically characterize the PEG-hTNFas, toxicity analyses after a
single high dose of PEG-TNFa and a prolonged PEG-TNFa treatment;
2) define TNFa anti-cancer features, analyses of: a)anti-tumor efficacies in
syngeneic and athymic mice with B16 melanomas, b)affinities of the PEG- hTNFas
for hTNF receptors I and II (prerequisite for clinical trials); and
3) determine the anti-human tumor efficacies of these PEG-hTNFas, treatment of
athymic mice bearing human colon carcinomas.
PROPOSED COMMERCIAL APPLICATION:
This proposal focuses on the development of new therapeutic agents, PEG-hNTFas
effective against a wide range of solid tumors. Novel geatures of modified hTNFas
include the likelihood of a marked synergy with cytotoxic chemotherapeutic agents
and the potential to target the tumor vasculature and the host immune system.
Principal Investigator:
Mike A. Clark
Small Business Information at Submission:
PHOENIX PHARMACOLOGICS
ASTECC FACILITY #A-217 UNIVERSITY OF KENTUCKY LEXINGTON, KY 40506
EIN/Tax ID:
232927291
DUNS:
N/A
Number of Employees:
N/A
Woman-Owned:
No
Minority-Owned:
No
HUBZone-Owned:
No