Generation of a Monoclonal Antibody Agonist to Toll-Like Receptor 5

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$109,719.00
Award Year:
2009
Program:
SBIR
Phase:
Phase I
Contract:
1R43CA141912-01
Award Id:
93600
Agency Tracking Number:
CA141912
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
BUFFALO BIOLABS, LLC, 73 HIGH ST, BUFFALO, NY, 14203
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
830459546
Principal Investigator:
OLGACHERNOVA
(718) 849-6810
OCHERNOVA@CBIOLABS.COM
Business Contact:
LINDAWEBSTER
() -
lwebster@cbiolabs.com
Research Institute:
n/a
Abstract
DESCRIPTION (provided by applicant): Systemic treatment with the bacterial flagellin protein, a Toll-like receptor 5 (TLR5) agonist, provides protection against high dose radiation through activation of nuclear factor-(B (NF-(B). NF-(B signaling induces mu ltiple factors that contribute to cell survival and tissue regeneration, including apoptosis inhibitors, reactive oxygen species scavengers, and cytokines. We have engineered CBLB502, an optimized flagellin derivative with reduced immunogenicity, for devel opment as a radioprotectant. While CBLB502 is currently in Phase 1 trials for biodefense applications, it is also expected to have a wide range of medical applications, including reduction of the adverse side effects of anti-cancer radio- and chemotherapy. However, repeated administration of CBLB502 could induce a neutralizing immune response that would limit its effectiveness. To develop alternative TLR5 agonists with reduced immunogenicity, we generated monoclonal anti-human-TLR5 antibodies that activate TLR5 upon binding. This proposal is focused on detailed functional and immunochemical characterization of the generated agonistic antibodies in order to select the candidates that most potently and specifically activate TLR5 in both epithelial and monocyti c cells of human origin and also activate TLR5 from other species commonly used in pre-clinical drug evaluation. In the next phase of the project, the selected antibodies will be evaluated for radioprotective efficacy in vivo. PUBLIC HEALTH RELEVANCE: P harmacological activation of TLR5 with CBLB502, a derivative of the bacterial flagellin protein, is a powerful approach to protection of sensitive tissues from acute radiation exposure and other types of stress. However, prolonged treatment with CBLB502 fo r some medical applications (such as protection of normal tissues during anti-cancer radiotherapy) could induce undesirable immune responses. Alternative TLR5 agonists with reduced immunogenicity, such as the agonistic antibodies that are the subject of th is proposal, would be ideal drugs for such applications, potentially leading to clinical impacts such as improvement of the therapeutic index of radiation therapy

* information listed above is at the time of submission.

Agency Micro-sites


SBA logo

Department of Agriculture logo

Department of Commerce logo

Department of Defense logo

Department of Education logo

Department of Energy logo

Department of Health and Human Services logo

Department of Homeland Security logo

Department of Transportation logo

Enviromental Protection Agency logo

National Aeronautics and Space Administration logo

National Science Foundation logo
US Flag An Official Website of the United States Government