Identifying the mechanism of resistance to immunotherapy in merkel cell carcinoma (for zachary reinstein)
Ended Project Grant Awarded Last action
- Award ID
- F30CA278298
- Recipient
-
Northwestern University UEI KG76WYENL5K1
- Awarding agency
-
National Cancer Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $307,313
Award facts
- Assistance listing
- 93.398 Cancer Research Manpower
- Completion date
- Place of performance
- Chicago, IL 60611, USA
Award details come from USAspending.gov.
Description
- Abstract
- Merkel cell carcinoma (MCC) is the most aggressive and fatal cancer on a case-by-case basis with rapidly rising incidence. Approximately 80% of MCC cases are caused by merkel cell polyomavirus, which expresses two viral oncogenes known as large t antigen and small t antigen that are required for clonal carcinogenesis. Notably, although MCC is highly aggressive, approximately 50% of patients treated with immune checkpoint blockade (ICB) respond to treatment. With approximately equal numbers of responsive patients to resistant patients and small, shared neoantigen repertoire, virus positive (VP) MCC serves as a model of t cell response in cancer. IT is unknown why some patients respond to ICB while others resist treatment. A critical unmet need is to develop treatments for patients with primary or acquired resistant to ICB. To elucidate this mechanism and identify biomarkers of ICB response, we have collected the largest clinically annotated database of primary MCC samples treated with ICB. We have identified a subset of t cells that drive ICB response. In this project, we will elucidate the mechanism by which these cells mediate response to ICB. We will spatially and functionally identify which receptor-ligand interactions are most critical in triggering a response by these t cells. Next, we will identify specific t cell receptors that recognize tumor antigens. Finally, we will characterize anti-MCC t cells in the tumor microenvironment that are causing this response. These results will validate the prognostic potential of these cells and identify the mechanism by which IT drives ICB response in VP MCC. My overall career goal is to become a successful, independent physician-scientist. The rigorous training plan proposed in this fellowship will allow me to achieve that goal by gaining research skills and knowledge in cellular immunology and bioinformatics. I will be mentored by DR. Jaehyuk choi, an expert physician-scientist in MCC, who has devised a training plan to develop all necessary research skills, communication skills and promote my professional development. This fellowship will broaden our understanding of MCC immunology and identify potential novel therapeutic strategies, as well as provide the necessary foundation for my future career as a physician-scientist.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $564 | |
| Amendment | $44,187 | |
| Amendment | $44,187 | |
| Amendment | $1,280 | |
| Amendment | $1,280 | |
| Amendment | $1,280 | |
| Amendment | $42,907 | |
| Amendment | $0 | |
| Amendment | $42,907 | |
| Amendment | $0 | |
| Amendment | $42,907 | |
| Amendment | $42,907 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Original award | $42,907 |
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Quick answers
Who received award F30CA278298?
F30CA278298 was awarded to Northwestern University by National Cancer Institute (National Institutes of Health) on July 23, 2024.
How much is award F30CA278298 worth?
$307,313 has been obligated on F30CA278298.
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