Adoptive transfer of cytotoxic T lymphocytes (CTL) represents an exciting mode of immunotherapy of human cancer. However, it is well known that large established tumors are very resistant to this type of immunotherapy. This proposal is based on our recent observation that targeting activation induced cytidine deaminase (AID) can render large established tumors to be rejected by CTL transfer. Further analysis of AID-eliminated, CTL-rejectable tumor cells revealed CD200 expression on tumor cells is responsible for tumor rejection. This proposal aims to explore the roles of CD200- CD200 receptor (R) pathway in T cell therapy of cancer. Our overall hypothesis is that enhancing CD200-CD200R interaction modulates tumor rejection by CTL through inhibition of the functions of tumor associated myeloid cells.
The specific aims of this proposal are: (1) to investigate the roles of CD200-CD200R interaction in CTL therapy of multiple lineages of experimental tumors;(2) to determine mechanisms by which CD200 expression on tumor cells impact T cell therapy of cancer and (3) to test if stimulating CD200R using agonistic antibody or CD200-Fc fusion protein can enhance CTL therapy of cancer. If successful, our proposed experiments will not only reveal new insights in CTL-mediated tumor rejection mechanisms, but also provide a basis for a novel therapy of human cancer.

Public Health Relevance

In this proposal we propose to study the roles of CD200-CD200 receptor interaction in cytotoxic T lymphocyte (CTL) therapy of cancer. Our proposed experiments will not only reveal new insights in CTL-mediated tumor rejection mechanisms, but also provide a basis for a novel therapy of human cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA138427-04
Application #
8204872
Study Section
Cancer Immunopathology and Immunotherapy Study Section (CII)
Program Officer
Mccarthy, Susan A
Project Start
2009-02-06
Project End
2014-12-31
Budget Start
2012-01-01
Budget End
2014-12-31
Support Year
4
Fiscal Year
2012
Total Cost
$241,530
Indirect Cost
$80,510
Name
Ohio State University
Department
Pathology
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
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