This application encompasses a 5-yeasr training program designed for the development of a pre-doctorial scientist. The candidate is currently enrolled in the Molecular and Cell Biology Program at Dartmouth College. Dr. Jose R Conejo-Garcia, assistant professor with a dual appointment in Microbiology and Immunology and in Medicine, will serve as her mentor. He has secured funding for the next 5 years and is also a member of the underrepresented minority group. An advisory committee of highly prominent scientists will provide further scientific and career advice through periodical meetings. The candidate will participate in a careful selection of course, seminars and scientific meetings as part of the training program. The broad goal of the research proposal is to elicit protective immunity against ovarian cancer. Our central hypothesis is that ovarian cancer-infiltrating dendritic cells can be activated in vivo and in situ to elicit efficient presentation of phagocytosed tumor antigens to anti-tumor T-cells in a therapeutically relevant manner.
The specific aims of the project are: 1. Determine how CD40/TLR agonists impact the immune response against ovarian cancer. 2. Define the molecular requirements for the immune response elicited by CD40/TLR agonists. 3. Determine the effect of CD40/TLR stimulation on adoptively transferred tumor-reactive T cells. This work will pave the way for a new generation of immunotherapies which, by complementing standard therapeutic approaches, will make a difference in the dismaying survival rates of ovarian cancer patients. Dartmouth Medical School is an ideal setting for the proposed training plan by incorporating the expertise of outstanding scientists with diverse backgrounds in a friendly environment an by offering access to state of the art technologies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31CA134188-02
Application #
8134922
Study Section
Special Emphasis Panel (ZRG1-DIG-E (29))
Program Officer
Bini, Alessandra M
Project Start
2009-09-01
Project End
2012-08-31
Budget Start
2010-09-01
Budget End
2011-08-31
Support Year
2
Fiscal Year
2010
Total Cost
$41,380
Indirect Cost
Name
Dartmouth College
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
Baird, Jason R; Fox, Barbara A; Sanders, Kiah L et al. (2013) Avirulent Toxoplasma gondii generates therapeutic antitumor immunity by reversing immunosuppression in the ovarian cancer microenvironment. Cancer Res 73:3842-51
Scarlett, Uciane K; Conejo-Garcia, Jose R (2012) Modulating the tumor immune microenvironment as an ovarian cancer treatment strategy. Expert Rev Obstet Gynecol 7:413-419
Scarlett, Uciane K; Rutkowski, Melanie R; Rauwerdink, Adam M et al. (2012) Ovarian cancer progression is controlled by phenotypic changes in dendritic cells. J Exp Med 209:495-506
Cubillos-Ruiz, Juan R; Martinez, Diana; Scarlett, Uciane K et al. (2010) CD277 is a negative co-stimulatory molecule universally expressed by ovarian cancer microenvironmental cells. Oncotarget 1:329-38
Nesbeth, Yolanda C; Martinez, Diana G; Toraya, Seiko et al. (2010) CD4+ T cells elicit host immune responses to MHC class II-negative ovarian cancer through CCL5 secretion and CD40-mediated licensing of dendritic cells. J Immunol 184:5654-62