Monday, December 1, 2025 12/1/2025

P38 MAPK is a molecular switch that controls the acquired resistance in adoptive cell therapy

Award Number: R37CA251318
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2020
PERIOD OF PERFORMANCE END DATE: 05/31/2025

Group Awards By:

View Award Description

P38 MAPK is a molecular switch that controls the acquired resistance in adoptive cell therapy - Project Summary A major obstacle to successful adoptive cell therapy (ACT) is the development of acquired resistance, which can occur due to cancer cells become invisible to tumor-specific T cells when cancer cells downregulate or lost the antigen(s) (refers to antigen-low/loss resistant tumor cells, or ALRs). In this proposal, we will explore the role of reprogramming of tumor microenvironment (TME) by p38 MAPK inhibition to promote a robust dendritic cell (DC)-driving anti-ALR immunity to prevent acquired resistance in ACT. In our in vivo preliminary studies, co-treatment with CAR T cells and Ralimetinib (a potent and selective inhibitor of p38 MAPK developed for cancer patients) confers immunogenic DC signature characteristics within TME. Strikingly, CAR T cell+Ralimetinib-treatment eradicated established tumors and resulted in long-term tumor-free survival by triggering a robust host anti-ALR immunity, whereas CAR T cell ACT alone recapitulated the clinical scenario of cancer relapse mediated by ALRs. Based on these novel findings, we hypothesize that p38 MAPK is a critical molecular switch that controls DC differentiation, where p38 inhibition promotes an immunogenic DC transcriptional program and induces potent anti-ALR immunity to prevent the acquired resistance in T cell therapy. Aim 1 will determine the role of NFκB/Stat5 signaling by repression of PPARγ in the molecular mechanisms of Ralimetinib-mediated DC enrichment. Aim 2 will determine the role of NFκB (p50)-dependent viral mimicry in DCs for ALR clearance after p38 inhibitor-treatment in vivo. This study may uncover a novel mechanism for preventing tumor relapse in ACT. Data from our proposed Aims may yield critically needed evidence that repurposing the clinically tested Ralimetinib from targeting p38 MAPK in tumor cells toward that of immune cells may induce a complete and durable response in ACT. This translationally relevant work could then lay the foundation for future clinical trials.


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: 2026 ( Subtotal = -$77,934 )
2026	2024	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	6	11/20/2025	NON-COMPETING CONTINUATION	-$77,934
														Subtotal = -$77,934

Issue Date FY: 2024 ( Subtotal = $350,064 )
2024	2024	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	000	6	6/12/2024	NON-COMPETING CONTINUATION	$350,064
														Subtotal = $350,064

Issue Date FY: 2023 ( Subtotal = $361,117 )
2023	2023	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	002	5	5/25/2023	NON-COMPETING CONTINUATION	$361,117
2023	2021	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	001	3	2/27/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$55,746
2023	2021	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cancer Biology Research	000	2	2/27/2023	NON-COMPETING CONTINUATION	-$55,746
														Subtotal = $361,117

Issue Date FY: 2022 ( Subtotal = $368,487 )
2022	2022	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	002	4	6/7/2022	NON-COMPETING CONTINUATION	$368,487
2022	2021	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Cancer Biology Research	001	3	3/3/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$124,000
2022	2021	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cancer Biology Research	000	2	3/3/2022	NON-COMPETING CONTINUATION	-$124,000
														Subtotal = $368,487

Issue Date FY: 2021 ( Subtotal = $354,563 )
2021	2021	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cancer Biology Research	000	2	5/18/2021	NON-COMPETING CONTINUATION	$354,563
														Subtotal = $354,563

Issue Date FY: 2020 ( Subtotal = $354,563 )
2020	2020	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cancer Biology Research	000	1	5/29/2020	NEW	$354,563
														Subtotal = $354,563

Grand Total All Awards = $1,710,860

Top

All Categories

About

Search

Reports

Data Submission

Award Information

P38 MAPK is a molecular switch that controls the acquired resistance in adoptive cell therapy

Award Number: R37CA251318

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2020

PERIOD OF PERFORMANCE END DATE: 05/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer