Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Elucidating and overcoming T cell dysfunction in pancreatic cancer

Award Number: R50CA293827
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/07/2025
PERIOD OF PERFORMANCE END DATE: 07/31/2030

Group Awards By:

View Award Description

Elucidating and overcoming T cell dysfunction in pancreatic cancer - PROJECT SUMMARY Pancreatic ductal adenocarcinoma (PDA) is a lethal disease notoriously resistant to therapy including immune checkpoint blockade. Meanwhile, immunotherapy targeting the PD-1:PD-L1 pathway is inducing stunning clinical outcomes in other advanced malignancies. However, the underlying mechanisms governing immune surveillance and resistance to a robust antitumor T cell response in pancreatic cancer are largely unknown. We are poised to identify how to safely promote T cell-mediated destruction of pancreatic cancer through 2 funded R01 applications and a collaborative P01 application. Our preliminary data support the hypothesis that immune- mediated pancreatic cancer eradication requires the following components: 1) a high affinity tumor specific T cell, 2) modification of suppressive intratumoral myeloid cells, and 3) overcoming chronic inflammatory and immunosuppressive signaling pathways. Notably our results demonstrate that developing combinatorial strategies to overcome endogenous T cell dysfunction in PDA may not be the same for enhancing cellular therapy using T cell receptor (TCR) engineered based approaches. Thus, the 3 funded projects are based on the development of highly faithful PDA animal models in which an endogenous or TCR engineered T cell response can be tracked longitudinally over time. The projects are aimed at uncovering novel mechanisms that interfere with the efficacy of combinatorial immunotherapies designed to engage the endogenous immunity (project 1) or TCR engineered T cell therapy (project 2 and 3). We will test novel combinatorial approaches to safely enhance the antitumor activity of a combination therapy that uses CD40 agonist, anti-PD-L1 (project 1) or abrogating TGFb signaling in TCR engineered T cells (Project 2) or the combination of TCR engineered T cell therapy and simultaneous modification of the desmoplastic tumor microenvironment (Project 3). Together the studies will identify characteristics of T cells and the tumor microenvironment that produce durable antitumor responses during immunotherapy.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $119,858 )
2025	2025	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Cancer Biology Research	000	1	8/5/2025	NEW	$119,858
														Subtotal = $119,858

Grand Total All Awards = $119,858

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Elucidating and overcoming T cell dysfunction in pancreatic cancer

Award Number: R50CA293827

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/07/2025

PERIOD OF PERFORMANCE END DATE: 07/31/2030

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer