Currently we have limited therapeutic options to treat patients with advanced non- resectable, recurrent and metastatic cancer. An innate immunity-mediated anticancer immunotherapy, alone or in combination with other therapies, represents a promising novel approach. Toll-like receptors (TLRs) play a crucial role in innate immunity and inflammation. We have found that members of the TLR receptor family are expressed not only in innate immune cells but also in different cancer cells. However, only TLR5 can be activated in both breast and prostate cancer cells to induce a robust immune response, which can effectively inhibit cancer cell proliferation. Furthermore, we recently discovered that a ten-amino acid long peptide (Tf10) derived from the bacterial protein flagellin (an agonist for TLR5) is able to target TLR5 on cancer cells and inducing anti- tumor responses. I now propose to use the Tf10 peptide/TLR5 interaction in the search for and design of novel therapeutic anti-cancer agents.

Public Health Relevance

We have found that members of the TLR receptor family are expressed not only in innate immune cells but also in different cancer cells. However, only TLR5 can be activated in both breast and prostate cancer cells to induce a robust immune response, which effectively can inhibit cancer cell proliferation. Furthermore, we recently discovered that a ten-amino acid long peptide (Tf10) derived from the bacterial protein flagellin (an agonist for TLR5) is able to target TLR5 on cancer cells and inducing anti-tumor responses.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21CA176698-01A1
Application #
8638356
Study Section
Special Emphasis Panel (ZCA1-SRLB-2 (O1))
Program Officer
Alley, Michael C
Project Start
2014-01-23
Project End
2015-12-31
Budget Start
2014-01-23
Budget End
2014-12-31
Support Year
1
Fiscal Year
2014
Total Cost
$123,203
Indirect Cost
$36,203
Name
Texas A&M University
Department
Biology
Type
Schools of Medicine
DUNS #
835607441
City
College Station
State
TX
Country
United States
Zip Code
77845
Zhao, Shu; Zhang, Yifan; Zhang, Qingyuan et al. (2014) Toll-like receptors and prostate cancer. Front Immunol 5:352
Fan, Yihui; Mao, Renfang; Yu, Yang et al. (2014) USP21 negatively regulates antiviral response by acting as a RIG-I deubiquitinase. J Exp Med 211:313-28