Here, we continue our study on two technologies we developed, chemotoxin and chemoarp. Both strategies are based on the nature of chemokines to deliver antigens to the cytosol of cells expressing respective chemokine receptors. Chemotoxin is a chimeric chemokine fused with toxic moieties to specifically kill cells expressing respective chemokine receptors. We used TARC-chemotoxin to successfully eradicate established leukemia or transiently deplete Treg cells in mice with breast cancer (Baatar et al, 2007a; 2009; Olkhanud et al., 2009). Chemoarp is a modified chemokine to specifically bind and deliver siRNA/miRNA into immune cells in vivo. We reported the efficacy of chemoarp by transiently inactivating IL10 and FoxP3 in CCR4+ Tregs in mice, which is sufficient to block lung metastasis (Biragyn et al., J. Immunotherapy, 2013). We also used chemoarp to deliver immunostimulatory CpG-ODN and activate antitumor responses of B cells in mice with breast cancer (Bodogai et al., 2013). Recently we initiated study to use chemoarp to improve efficacy of cancer vaccines we previously devised. We wanted to transiently modulate activity of several immune regulatory cells via delivering siRNA. Unfortunately, due to failure of our vaccine delivery apparatus, we could not continue the study until recently. We expect that the study will be completed in one year, which would further popularize the importance of our chemoarp technology. However, our technologies are being successfully utilized by others to publish a number of papers in collaboration with our laboratory, such as Dr. Rivas-Santiago (Mexican Institute of Social Security, Mexico) tested for prevention tuberculosis in mice (Cervantes-Villagrana et al., 2013); professors Nishioka and Sone (University of Tokushima, Japan) to alleviate asthma (Honjo et al., Respir. Investig., 2013); professors Markham from JHU to generate malaria vaccine (Luo et al., PlosOne, 2014; Geoghegan et al., Antimicrob. Agents, 2015); and Dr.Okuma in therapy of ATLL (Hiyoshi et al, Retrovirology, 2015).

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000444-08
Application #
9147301
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Aging
Department
Type
DUNS #
City
State
Country
Zip Code
Luo, Kun; Zhang, Hong; Zavala, Fidel et al. (2014) Fusion of antigen to a dendritic cell targeting chemokine combined with adjuvant yields a malaria DNA vaccine with enhanced protective capabilities. PLoS One 9:e90413
Biragyn, Arya; Bodogai, Monica; Olkhanud, Purevdorj B et al. (2013) Inhibition of lung metastasis by chemokine CCL17-mediated in vivo silencing of genes in CCR4+ Tregs. J Immunother 36:258-67
Honjo, Akifumi; Ogawa, Hirohisa; Azuma, Masahiko et al. (2013) Targeted reduction of CCR4? cells is sufficient to suppress allergic airway inflammation. Respir Investig 51:241-9
Cervantes-Villagrana, Alberto R; Hernández-Pando, Rogelio; Biragyn, Arya et al. (2013) Prime-boost BCG vaccination with DNA vaccines based in ?-defensin-2 and mycobacterial antigens ESAT6 or Ag85B improve protection in a tuberculosis experimental model. Vaccine 31:676-84
Baatar, Dolgor; Olkhanud, Purevdorj B; Wells, Valerie et al. (2009) Tregs utilize beta-galactoside-binding protein to transiently inhibit PI3K/p21ras activity of human CD8+ T cells to block their TCR-mediated ERK activity and proliferation. Brain Behav Immun 23:1028-37
Olkhanud, Purevdorj B; Baatar, Dolgor; Bodogai, Monica et al. (2009) Breast cancer lung metastasis requires expression of chemokine receptor CCR4 and regulatory T cells. Cancer Res 69:5996-6004