The long-term objective of these studies is to determine whether a unique set of CD8 T cells can play a role in cancer therapy using the immune system. Specifically, we and others found that CD8 (killer) T cells that secrete a chemical substance (cytokine) known as interleukin-17 (IL-17) appear to last longer and function better than those that secrete other cytokines. We plan to determine how these cells (called Tc17) kill tumors, and whether they absolutely need IL-17 to work. Next, we plan to figure out the best way to make these cells, focusing on whether the target they recognize (antigen) plays a major role in that process. Finally, we found that Tc17 cells show an extremely interesting property that might be important for their superior anti-tumor function: in animals these cells convert, or flip the cytokines they produce. This conversion process is fascinating, and a better understanding of it might be important in understanding how other tumor treatments that use the immune system work. These experiments will not be undertaken in a vacuum;several groups, including ours have already showed that CD8 T cells that make IL-17 have superior anti-tumor activity in animals. Thus, these studies are designed to follow up on those intriguing results in an effort to engineer and understand a superior method for cancer treatment.

Public Health Relevance

This project is directly relevant to cancer treatment, a significant public health problem. Using an animal model, we will investigate a new method for cancer treatment that uses a patient's own immune cells to attack tumors;these cells will be removed from the body, manipulated in a novel way, and then returned. If our animal studies are successful, similar methods can be readily tested in humans.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA154555-02
Application #
8434218
Study Section
Cancer Immunopathology and Immunotherapy Study Section (CII)
Program Officer
Mccarthy, Susan A
Project Start
2012-03-01
Project End
2017-02-28
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
2
Fiscal Year
2013
Total Cost
$315,981
Indirect Cost
$120,931
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Sharabi, Andrew B; Nirschl, Christopher J; Kochel, Christina M et al. (2015) Stereotactic Radiation Therapy Augments Antigen-Specific PD-1-Mediated Antitumor Immune Responses via Cross-Presentation of Tumor Antigen. Cancer Immunol Res 3:345-55