The survival rate of colorectal cancer and breast cancer as measured by Mortality to incidence ratios (MIRs) is worse among American Indian and Alaskan Native (AI/AN) population as compared to the white population. AI/AN individuals are more likely to be diagnosed with late-stage disease and this leads to poor treatment outcomes and increased mortality. These disparities in cancer within the AI/AN population is compounded by resistance to existing therapies and a high relapse rates among patients. Thus, there is a need to develop novel therapies to cure treatment resistant breast cancer. This study aims to alleviate these disparities faced by the AI/AN population by testing out a new cellular therapeutic approach to treat cancer. NK cells are a key component of the innate immune system and play an important role in early immunity to cancer by killing a variety of tumors. Adoptive transfer of NK cells and NK cell lines is a significant mode of cellular therapy that is being tested in various clinical trials to treat cancers. Efforts are being made to enhance the cytotoxic effects of NK cells and NK cell lines by treating them ex-vivo with different modulating agents. In our recent study, we found that NK cells when treated with reovirus become activated and show an enhanced cytotoxicity against tumor cells. In this project, we will test the ability of reovirus to increase the cytotoxicity of a NK cell line, NK-92MI, against human colorectal cancer cell line-DLD-1. Subsequently, we will perform an adoptive transfer of the reovirus activated NK-92MI cells to treat mice bearing DLD-1 tumors. Results from this study will increase our understanding of NK cell mediated antitumor response and help us develop new strategies to enhance NK cell cytotoxic functions for cancer treatment. Successful completion of this study will provide us with a novel cellular anti-cancer therapy with a potential to be translated into the clinic.

Agency
National Institute of Health (NIH)
Institute
National Institute on Minority Health and Health Disparities (NIMHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
1U54MD012388-01
Application #
9449734
Study Section
Special Emphasis Panel (ZMD1)
Project Start
Project End
Budget Start
2017-09-20
Budget End
2018-06-30
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Northern Arizona University
Department
Type
DUNS #
806345542
City
Flagstaff
State
AZ
Country
United States
Zip Code
86011
Trotter 2nd, Robert T; Lininger, Monica R; Camplain, Ricky et al. (2018) A Survey of Health Disparities, Social Determinants of Health, and Converging Morbidities in a County Jail: A Cultural-Ecological Assessment of Health Conditions in Jail Populations. Int J Environ Res Public Health 15:
Varadaraj, Archana; Magdaleno, Carina; Mythreye, Karthikeyan (2018) Deoxycholate Fractionation of Fibronectin (FN) and Biotinylation Assay to Measure Recycled FN Fibrils in Epithelial Cells. Bio Protoc 8:
Trotter Ii, Robert T; Camplain, Ricky; Eaves, Emery R et al. (2018) Health Disparities and Converging Epidemics in Jail Populations: Protocol for a Mixed-Methods Study. JMIR Res Protoc 7:e10337