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

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
93600
Program Year/Program:
2009 / SBIR
Agency Tracking Number:
CA141912
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
BUFFALO BIOLABS, LLC
BUFFALO BIOLABS, LLC 73 HIGH ST BUFFALO, NY 14203-1149
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2009
Title: Generation of a Monoclonal Antibody Agonist to Toll-Like Receptor 5
Agency: HHS
Contract: 1R43CA141912-01
Award Amount: $109,719.00
 

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

Principal Investigator:

Olga B. Chernova
7188496810
OCHERNOVA@CBIOLABS.COM

Business Contact:

Linda Webster
lwebster@cbiolabs.com
Small Business Information at Submission:

BUFFALO BIOLABS, LLC
BUFFALO BIOLABS, LLC 73 HIGH ST BUFFALO, NY 14203

EIN/Tax ID: 126472149
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No